---
_id: '12802'
abstract:
- lang: eng
text: Little is known about the critical metabolic changes that neural cells have
to undergo during development and how temporary shifts in this program can influence
brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5,
a transporter of metabolically essential large neutral amino acids (LNAAs), lead
to autism, we employed metabolomic profiling to study the metabolic states of
the cerebral cortex across different developmental stages. We found that the forebrain
undergoes significant metabolic remodeling throughout development, with certain
groups of metabolites showing stage-specific changes, but what are the consequences
of perturbing this metabolic program? By manipulating Slc7a5 expression in neural
cells, we found that the metabolism of LNAAs and lipids are interconnected in
the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state,
leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific
alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.
acknowledged_ssus:
- _id: PreCl
- _id: EM-Fac
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Freeman and V. Voronin for technical assistance, S. Deixler,
A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal
colony. We thank L. Andersen and J. Sonntag, who were involved in generating the
MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance
with the proteomic analysis, as well as the ISTA electron microscopy and Imaging
and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed
by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge
the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular
metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was
performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated
using Biorender.com. This work was supported by the Austrian Science Fund (FWF,
DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Daniel
full_name: Malzl, Daniel
last_name: Malzl
- first_name: Maria
full_name: Gerykova Bujalkova, Maria
last_name: Gerykova Bujalkova
- first_name: Mateja
full_name: Smogavec, Mateja
last_name: Smogavec
- first_name: Lena A.
full_name: Schwarz, Lena A.
last_name: Schwarz
- first_name: Sarah
full_name: Gorkiewicz, Sarah
id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f
last_name: Gorkiewicz
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Christian
full_name: Knittl-Frank, Christian
last_name: Knittl-Frank
- first_name: Marianna
full_name: Tassinari, Marianna
id: 7af593f1-d44a-11ed-bf94-a3646a6bb35e
last_name: Tassinari
- first_name: Nuno
full_name: Maulide, Nuno
last_name: Maulide
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Jörg
full_name: Menche, Jörg
last_name: Menche
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal
neuronal excitability and survival. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037
apa: Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz,
L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal
excitability and survival. Cell. Elsevier. https://doi.org/10.1016/j.cell.2023.02.037
chicago: Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova,
Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino
Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell. Elsevier,
2023. https://doi.org/10.1016/j.cell.2023.02.037.
ieee: L. Knaus et al., “Large neutral amino acid levels tune perinatal neuronal
excitability and survival,” Cell, vol. 186, no. 9. Elsevier, p. 1950–1967.e25,
2023.
ista: Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA,
Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke
T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels
tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.
mla: Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal
Excitability and Survival.” Cell, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25,
doi:10.1016/j.cell.2023.02.037.
short: L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A.
Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N.
Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25.
corr_author: '1'
date_created: 2023-04-05T08:15:40Z
date_published: 2023-04-27T00:00:00Z
date_updated: 2026-04-14T08:34:36Z
day: '27'
ddc:
- '570'
department:
- _id: SiHi
- _id: GaNo
doi: 10.1016/j.cell.2023.02.037
ec_funded: 1
external_id:
isi:
- '000991468700001'
pmid:
- '36996814'
file:
- access_level: open_access
checksum: 47e94fbe19e86505b429cb7a5b503ce6
content_type: application/pdf
creator: dernst
date_created: 2023-05-02T09:26:21Z
date_updated: 2023-05-02T09:26:21Z
file_id: '12889'
file_name: 2023_Cell_Knaus.pdf
file_size: 15712841
relation: main_file
success: 1
file_date_updated: 2023-05-02T09:26:21Z
has_accepted_license: '1'
intvolume: ' 186'
isi: 1
issue: '9'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 1950-1967.e25
pmid: 1
project:
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
publication: Cell
publication_identifier:
issn:
- 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/feed-them-or-lose-them/
record:
- id: '19557'
relation: dissertation_contains
status: public
- id: '13107'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Large neutral amino acid levels tune perinatal neuronal excitability and survival
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 186
year: '2023'
...
---
_id: '11449'
abstract:
- lang: eng
text: Mutations are acquired frequently, such that each cell's genome inscribes
its history of cell divisions. Common genomic alterations involve loss of heterozygosity
(LOH). LOH accumulates throughout the genome, offering large encoding capacity
for inferring cell lineage. Using only single-cell RNA sequencing (scRNA-seq)
of mouse brain cells, we found that LOH events spanning multiple genes are revealed
as tracts of monoallelically expressed, constitutionally heterozygous single-nucleotide
variants (SNVs). We simultaneously inferred cell lineage and marked developmental
time points based on X chromosome inactivation and the total number of LOH events
while identifying cell types from gene expression patterns. Our results are consistent
with progenitor cells giving rise to multiple cortical cell types through stereotyped
expansion and distinct waves of neurogenesis. This type of retrospective analysis
could be incorporated into scRNA-seq pipelines and, compared with experimental
approaches for determining lineage in model organisms, is applicable where genetic
engineering is prohibited, such as humans.
acknowledgement: D.J.A. thanks Wayne K. Potts, Alan R. Rogers, Kristen Hawkes, Ryk
Ward, and Jon Seger for inspiring a young undergraduate to apply evolutionary theory
to intraorganism development. Supported by the Paul G. Allen Frontiers Group (University
of Washington); NIH R00HG010152 (Dartmouth); and NÖ Forschung und Bildung n[f+b]
life science call grant (C13-002) and the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation program 725780 LinPro
to S.H.
article_processing_charge: No
article_type: original
author:
- first_name: Donovan J.
full_name: Anderson, Donovan J.
last_name: Anderson
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Aaron
full_name: Mckenna, Aaron
last_name: Mckenna
- first_name: Jay
full_name: Shendure, Jay
last_name: Shendure
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Marshall S.
full_name: Horwitz, Marshall S.
last_name: Horwitz
citation:
ama: Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous
brain cell type and lineage determined by scRNA-seq reveals stereotyped cortical
development. Cell Systems. 2022;13(6):438-453.e5. doi:10.1016/j.cels.2022.03.006
apa: Anderson, D. J., Pauler, F., Mckenna, A., Shendure, J., Hippenmeyer, S., &
Horwitz, M. S. (2022). Simultaneous brain cell type and lineage determined by
scRNA-seq reveals stereotyped cortical development. Cell Systems. Elsevier.
https://doi.org/10.1016/j.cels.2022.03.006
chicago: Anderson, Donovan J., Florian Pauler, Aaron Mckenna, Jay Shendure, Simon
Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Brain Cell Type and Lineage
Determined by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems.
Elsevier, 2022. https://doi.org/10.1016/j.cels.2022.03.006.
ieee: D. J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, and M.
S. Horwitz, “Simultaneous brain cell type and lineage determined by scRNA-seq
reveals stereotyped cortical development,” Cell Systems, vol. 13, no. 6.
Elsevier, p. 438–453.e5, 2022.
ista: Anderson DJ, Pauler F, Mckenna A, Shendure J, Hippenmeyer S, Horwitz MS. 2022.
Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped
cortical development. Cell Systems. 13(6), 438–453.e5.
mla: Anderson, Donovan J., et al. “Simultaneous Brain Cell Type and Lineage Determined
by ScRNA-Seq Reveals Stereotyped Cortical Development.” Cell Systems, vol.
13, no. 6, Elsevier, 2022, p. 438–453.e5, doi:10.1016/j.cels.2022.03.006.
short: D.J. Anderson, F. Pauler, A. Mckenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz,
Cell Systems 13 (2022) 438–453.e5.
date_created: 2022-06-19T22:01:57Z
date_published: 2022-06-15T00:00:00Z
date_updated: 2025-04-14T07:43:05Z
day: '15'
department:
- _id: SiHi
doi: 10.1016/j.cels.2022.03.006
ec_funded: 1
external_id:
isi:
- '000814124400002'
pmid:
- '35452605'
intvolume: ' 13'
isi: 1
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.cels.2022.03.006
month: '06'
oa: 1
oa_version: Published Version
page: 438-453.e5
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
publication: Cell Systems
publication_identifier:
eissn:
- 2405-4720
issn:
- 2405-4712
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Simultaneous brain cell type and lineage determined by scRNA-seq reveals stereotyped
cortical development
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 13
year: '2022'
...
---
_id: '11460'
abstract:
- lang: eng
text: "Background: Proper cerebral cortical development depends on the tightly orchestrated
migration of newly born neurons from the inner ventricular and subventricular
zones to the outer cortical plate. Any disturbance in this process during prenatal
stages may lead to neuronal migration disorders (NMDs), which can vary in extent
from focal to global. Furthermore, NMDs show a substantial comorbidity with other
neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous
work demonstrated focal neuronal migration defects in mice carrying loss-of-function
alleles of the recognized autism risk gene WDFY3. However, the cellular origins
of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide
critical insight into WDFY3-dependent disease pathology.\r\nMethods: Here, in
an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic
analysis with double markers (MADM). MADM technology enabled us to genetically
distinctly track and phenotypically analyze mutant and wild-type cells concomitantly
in vivo using immunofluorescent techniques.\r\nResults: We revealed a cell autonomous
requirement of WDFY3 for accurate laminar positioning of cortical projection neurons
and elimination of mispositioned cells during early postnatal life. In addition,
we identified significant deviations in dendritic arborization, as well as synaptic
density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant
neurons in Wdfy3-MADM reporter mice at postnatal stages.\r\nLimitations: While
Wdfy3 mutant mice have provided valuable insight into prenatal aspects of ASD
pathology that remain inaccessible to investigation in humans, like most animal
models, they do not a perfectly replicate all aspects of human ASD biology. The
lack of human data makes it indeterminate whether morphological deviations described
here apply to ASD patients or some of the other neurodevelopmental conditions
associated with WDFY3 mutation.\r\nConclusions: Our genetic approach revealed
several cell autonomous requirements of WDFY3 in neuronal development that could
underlie the pathogenic mechanisms of WDFY3-related neurodevelopmental conditions.
The results are also consistent with findings in other ASD animal models and patients
and suggest an important role for WDFY3 in regulating neuronal function and interconnectivity
in postnatal life."
acknowledgement: "This study was funded by NIMH R21MH115347 to KSZ. KSZ is further
supported by Shriners Hospitals for Children.\r\nWe would like to thank Angelo Harlan
de Crescenzo for early contributions to this project."
article_number: '27'
article_processing_charge: No
article_type: original
author:
- first_name: Zachary A.
full_name: Schaaf, Zachary A.
last_name: Schaaf
- first_name: Lyvin
full_name: Tat, Lyvin
last_name: Tat
- first_name: Noemi
full_name: Cannizzaro, Noemi
last_name: Cannizzaro
- first_name: Ralph
full_name: Green, Ralph
last_name: Green
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Konstantinos S.
full_name: Zarbalis, Konstantinos S.
last_name: Zarbalis
citation:
ama: Schaaf ZA, Tat L, Cannizzaro N, et al. WDFY3 mutation alters laminar position
and morphology of cortical neurons. Molecular Autism. 2022;13. doi:10.1186/s13229-022-00508-3
apa: Schaaf, Z. A., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer,
S., & Zarbalis, K. S. (2022). WDFY3 mutation alters laminar position and morphology
of cortical neurons. Molecular Autism. Springer Nature. https://doi.org/10.1186/s13229-022-00508-3
chicago: Schaaf, Zachary A., Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke,
Simon Hippenmeyer, and Konstantinos S. Zarbalis. “WDFY3 Mutation Alters Laminar
Position and Morphology of Cortical Neurons.” Molecular Autism. Springer
Nature, 2022. https://doi.org/10.1186/s13229-022-00508-3.
ieee: Z. A. Schaaf et al., “WDFY3 mutation alters laminar position and morphology
of cortical neurons,” Molecular Autism, vol. 13. Springer Nature, 2022.
ista: Schaaf ZA, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis
KS. 2022. WDFY3 mutation alters laminar position and morphology of cortical neurons.
Molecular Autism. 13, 27.
mla: Schaaf, Zachary A., et al. “WDFY3 Mutation Alters Laminar Position and Morphology
of Cortical Neurons.” Molecular Autism, vol. 13, 27, Springer Nature, 2022,
doi:10.1186/s13229-022-00508-3.
short: Z.A. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer,
K.S. Zarbalis, Molecular Autism 13 (2022).
date_created: 2022-06-23T14:28:55Z
date_published: 2022-06-22T00:00:00Z
date_updated: 2025-06-11T13:34:57Z
day: '22'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1186/s13229-022-00508-3
external_id:
isi:
- '000814641400001'
pmid:
- '35733184'
file:
- access_level: open_access
checksum: 525d2618e855139089bbfc3e3d49d1b2
content_type: application/pdf
creator: dernst
date_created: 2022-06-24T08:22:59Z
date_updated: 2022-06-24T08:22:59Z
file_id: '11461'
file_name: 2022_MolecularAutism_Schaaf.pdf
file_size: 7552298
relation: main_file
success: 1
file_date_updated: 2022-06-24T08:22:59Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
keyword:
- Psychiatry and Mental health
- Developmental Biology
- Developmental Neuroscience
- Molecular Biology
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Molecular Autism
publication_identifier:
issn:
- 2040-2392
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: erratum
url: https://doi.org/10.1186/s13229-023-00539-4
scopus_import: '1'
status: public
title: WDFY3 mutation alters laminar position and morphology of cortical neurons
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2022'
...
---
_id: '12282'
abstract:
- lang: eng
text: From a simple thought to a multicellular movement
acknowledgement: The authors want to thank Professors Carrie Bernecky, Tom Henzinger,
Martin Loose and Gaia Novarino for accepting to be interviewed, thus giving significant
contribution to the discussion that lead to this article.
article_number: '260017'
article_processing_charge: No
article_type: letter_note
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Melissa A
full_name: Stouffer, Melissa A
id: 4C9372C4-F248-11E8-B48F-1D18A9856A87
last_name: Stouffer
- first_name: Irene
full_name: Vercellino, Irene
id: 3ED6AF16-F248-11E8-B48F-1D18A9856A87
last_name: Vercellino
orcid: 0000-0001-5618-3449
citation:
ama: Amberg N, Stouffer MA, Vercellino I. Operation STEM fatale – how an equity,
diversity and inclusion initiative has brought us to reflect on the current challenges
in cell biology and science as a whole. Journal of Cell Science. 2022;135(8).
doi:10.1242/jcs.260017
apa: Amberg, N., Stouffer, M. A., & Vercellino, I. (2022). Operation STEM fatale
– how an equity, diversity and inclusion initiative has brought us to reflect
on the current challenges in cell biology and science as a whole. Journal of
Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.260017
chicago: Amberg, Nicole, Melissa A Stouffer, and Irene Vercellino. “Operation STEM
Fatale – How an Equity, Diversity and Inclusion Initiative Has Brought Us to Reflect
on the Current Challenges in Cell Biology and Science as a Whole.” Journal
of Cell Science. The Company of Biologists, 2022. https://doi.org/10.1242/jcs.260017.
ieee: N. Amberg, M. A. Stouffer, and I. Vercellino, “Operation STEM fatale – how
an equity, diversity and inclusion initiative has brought us to reflect on the
current challenges in cell biology and science as a whole,” Journal of Cell
Science, vol. 135, no. 8. The Company of Biologists, 2022.
ista: Amberg N, Stouffer MA, Vercellino I. 2022. Operation STEM fatale – how an
equity, diversity and inclusion initiative has brought us to reflect on the current
challenges in cell biology and science as a whole. Journal of Cell Science. 135(8),
260017.
mla: Amberg, Nicole, et al. “Operation STEM Fatale – How an Equity, Diversity and
Inclusion Initiative Has Brought Us to Reflect on the Current Challenges in Cell
Biology and Science as a Whole.” Journal of Cell Science, vol. 135, no.
8, 260017, The Company of Biologists, 2022, doi:10.1242/jcs.260017.
short: N. Amberg, M.A. Stouffer, I. Vercellino, Journal of Cell Science 135 (2022).
corr_author: '1'
date_created: 2023-01-16T10:03:14Z
date_published: 2022-04-19T00:00:00Z
date_updated: 2024-10-09T21:03:55Z
day: '19'
department:
- _id: SiHi
- _id: LeSa
doi: 10.1242/jcs.260017
external_id:
isi:
- '000798123600015'
pmid:
- '35438168'
intvolume: ' 135'
isi: 1
issue: '8'
language:
- iso: eng
month: '04'
oa_version: None
pmid: 1
publication: Journal of Cell Science
publication_identifier:
eissn:
- 1477-9137
issn:
- 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: Operation STEM fatale – how an equity, diversity and inclusion initiative has
brought us to reflect on the current challenges in cell biology and science as a
whole
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 135
year: '2022'
...
---
_id: '12283'
abstract:
- lang: eng
text: Neurons extend axons to form the complex circuitry of the mature brain. This
depends on the coordinated response and continuous remodelling of the microtubule
and F-actin networks in the axonal growth cone. Growth cone architecture remains
poorly understood at nanoscales. We therefore investigated mouse hippocampal neuron
growth cones using cryo-electron tomography to directly visualise their three-dimensional
subcellular architecture with molecular detail. Our data showed that the hexagonal
arrays of actin bundles that form filopodia penetrate and terminate deep within
the growth cone interior. We directly observed the modulation of these and other
growth cone actin bundles by alteration of individual F-actin helical structures.
Microtubules with blunt, slightly flared or gently curved ends predominated in
the growth cone, frequently contained lumenal particles and exhibited lattice
defects. Investigation of the effect of absence of doublecortin, a neurodevelopmental
cytoskeleton regulator, on growth cone cytoskeleton showed no major anomalies
in overall growth cone organisation or in F-actin subpopulations. However, our
data suggested that microtubules sustained more structural defects, highlighting
the importance of microtubule integrity during growth cone migration.
acknowledgement: "J.A. was supported by a grant from the Medical Research Council
(MRC), UK (MR/R000352/1) to C.A.M. Cryo-EM data were collected on equipment funded
by the Wellcome Trust, UK (079605/Z/06/Z) and the Biotechnology and Biological Sciences
Research Council (BBSRC) UK (BB/L014211/1). F.F.’s salary and institute were supported
by Inserm (Institut National de la Santé et de la Recherche Médicale), CNRS (Centre
National de la Recherche Scientifique) and Sorbonne Université. F.F.’s group was
particularly supported by Agence Nationale de la\r\nRecherche (ANR-16-CE16-0011-03)
and Seventh Framework Programme (EUHEALTH-\r\n2013, DESIRE, N° 60253; also funding
M.S.’s salary) and the European Cooperation in Science and Technology (COST Action
CA16118). Open Access funding provided by Birkbeck College: Birkbeck University
of London. Deposited in PMC for immediate release."
article_number: '259234'
article_processing_charge: No
article_type: original
author:
- first_name: Joseph
full_name: Atherton, Joseph
last_name: Atherton
- first_name: Melissa A
full_name: Stouffer, Melissa A
id: 4C9372C4-F248-11E8-B48F-1D18A9856A87
last_name: Stouffer
- first_name: Fiona
full_name: Francis, Fiona
last_name: Francis
- first_name: Carolyn A.
full_name: Moores, Carolyn A.
last_name: Moores
citation:
ama: Atherton J, Stouffer MA, Francis F, Moores CA. Visualising the cytoskeletal
machinery in neuronal growth cones using cryo-electron tomography. Journal
of Cell Science. 2022;135(7). doi:10.1242/jcs.259234
apa: Atherton, J., Stouffer, M. A., Francis, F., & Moores, C. A. (2022). Visualising
the cytoskeletal machinery in neuronal growth cones using cryo-electron tomography.
Journal of Cell Science. The Company of Biologists. https://doi.org/10.1242/jcs.259234
chicago: Atherton, Joseph, Melissa A Stouffer, Fiona Francis, and Carolyn A. Moores.
“Visualising the Cytoskeletal Machinery in Neuronal Growth Cones Using Cryo-Electron
Tomography.” Journal of Cell Science. The Company of Biologists, 2022.
https://doi.org/10.1242/jcs.259234.
ieee: J. Atherton, M. A. Stouffer, F. Francis, and C. A. Moores, “Visualising the
cytoskeletal machinery in neuronal growth cones using cryo-electron tomography,”
Journal of Cell Science, vol. 135, no. 7. The Company of Biologists, 2022.
ista: Atherton J, Stouffer MA, Francis F, Moores CA. 2022. Visualising the cytoskeletal
machinery in neuronal growth cones using cryo-electron tomography. Journal of
Cell Science. 135(7), 259234.
mla: Atherton, Joseph, et al. “Visualising the Cytoskeletal Machinery in Neuronal
Growth Cones Using Cryo-Electron Tomography.” Journal of Cell Science,
vol. 135, no. 7, 259234, The Company of Biologists, 2022, doi:10.1242/jcs.259234.
short: J. Atherton, M.A. Stouffer, F. Francis, C.A. Moores, Journal of Cell Science
135 (2022).
date_created: 2023-01-16T10:03:24Z
date_published: 2022-04-01T00:00:00Z
date_updated: 2023-08-04T10:28:34Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1242/jcs.259234
external_id:
isi:
- '000783840400010'
pmid:
- '35383828'
file:
- access_level: open_access
checksum: 4346ed32cb7c89a8ca051c7da68a9a1c
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T11:41:01Z
date_updated: 2023-01-30T11:41:01Z
file_id: '12461'
file_name: 2022_JourCellBiology_Atherton.pdf
file_size: 13868733
relation: main_file
success: 1
file_date_updated: 2023-01-30T11:41:01Z
has_accepted_license: '1'
intvolume: ' 135'
isi: 1
issue: '7'
keyword:
- Cell Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Cell Science
publication_identifier:
eissn:
- 1477-9137
issn:
- 0021-9533
publication_status: published
publisher: The Company of Biologists
quality_controlled: '1'
scopus_import: '1'
status: public
title: Visualising the cytoskeletal machinery in neuronal growth cones using cryo-electron
tomography
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 135
year: '2022'
...
---
_id: '10792'
abstract:
- lang: eng
text: "Background\r\nProper cerebral cortical development depends on the tightly
orchestrated migration of newly born neurons from the inner ventricular and subventricular
zones to the outer cortical plate. Any disturbance in this process during prenatal
stages may lead to neuronal migration disorders (NMDs), which can vary in extent
from focal to global. Furthermore, NMDs show a substantial comorbidity with other
neurodevelopmental disorders, notably autism spectrum disorders (ASDs). Our previous
work demonstrated focal neuronal migration defects in mice carrying loss-of-function
alleles of the recognized autism risk gene WDFY3. However, the cellular origins
of these defects in Wdfy3 mutant mice remain elusive and uncovering it will provide
critical insight into WDFY3-dependent disease pathology .\r\nMethods\r\nHere,
in an effort to untangle the origins of NMDs in Wdfy3lacZ mice, we employed mosaic
analysis with double markers (MADM). MADM technology enabled us to genetically
distinctly track and phenotypically analyze mutant and wild type cells concomitantly
in vivo using immunofluorescent techniques.\r\nResults\r\nWe revealed a cell autonomous
requirement of WDFY3 for accurate laminar positioning of cortical projection neurons
and elimination of mispositioned cells during early postnatal life. In addition,
we identified significant deviations in dendritic arborization, as well as synaptic
density and morphology between wild type, heterozygous, and homozygous Wdfy3 mutant
neurons in Wdfy3-MADM reporter mice at postnatal stages. Limitations While Wdfy3
mutant mice have provided valuable insight into prenatal aspects of ASD pathology
that remain inaccessible to investigation in humans, like most animal models,
they do not a perfectly replicate all aspects of human ASD biology. The lack of
human data makes it indeterminate whether morphological deviations described here
apply to ASD patients.\r\nConclusions\r\n\uFEFFOur genetic approach revealed several
cell autonomous requirements of Wdfy3 in neuronal development that could underly
the pathogenic mechanisms of WDFY3-related ASD conditions. The results are also
consistent with findings in other ASD animal models and patients and suggest an
important role for Wdfy3 in regulating neuronal function and interconnectivity
in postnatal life."
article_processing_charge: No
author:
- first_name: Zachary
full_name: Schaaf, Zachary
last_name: Schaaf
- first_name: Lyvin
full_name: Tat, Lyvin
last_name: Tat
- first_name: Noemi
full_name: Cannizzaro, Noemi
last_name: Cannizzaro
- first_name: Ralph
full_name: Green, Ralph
last_name: Green
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: K
full_name: Zarbalis, K
last_name: Zarbalis
citation:
ama: Schaaf Z, Tat L, Cannizzaro N, et al. WDFY3 cell autonomously controls neuronal
migration. doi:10.21203/rs.3.rs-1316167/v1
apa: Schaaf, Z., Tat, L., Cannizzaro, N., Green, R., Rülicke, T., Hippenmeyer, S.,
& Zarbalis, K. (n.d.). WDFY3 cell autonomously controls neuronal migration.
Research Square. https://doi.org/10.21203/rs.3.rs-1316167/v1
chicago: Schaaf, Zachary, Lyvin Tat, Noemi Cannizzaro, Ralph Green, Thomas Rülicke,
Simon Hippenmeyer, and K Zarbalis. “WDFY3 Cell Autonomously Controls Neuronal
Migration.” Research Square, n.d. https://doi.org/10.21203/rs.3.rs-1316167/v1.
ieee: Z. Schaaf et al., “WDFY3 cell autonomously controls neuronal migration.”
Research Square.
ista: Schaaf Z, Tat L, Cannizzaro N, Green R, Rülicke T, Hippenmeyer S, Zarbalis
K. WDFY3 cell autonomously controls neuronal migration. 10.21203/rs.3.rs-1316167/v1.
mla: Schaaf, Zachary, et al. WDFY3 Cell Autonomously Controls Neuronal Migration.
Research Square, doi:10.21203/rs.3.rs-1316167/v1.
short: Z. Schaaf, L. Tat, N. Cannizzaro, R. Green, T. Rülicke, S. Hippenmeyer, K.
Zarbalis, (n.d.).
date_created: 2022-02-25T07:53:26Z
date_published: 2022-02-16T00:00:00Z
date_updated: 2023-10-17T13:06:52Z
day: '16'
department:
- _id: SiHi
doi: 10.21203/rs.3.rs-1316167/v1
external_id:
pmid:
- PPR454733
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.21203/rs.3.rs-1316167/v1
month: '02'
oa: 1
oa_version: Preprint
page: '30'
pmid: 1
publication_identifier:
eissn:
- 2693-5015
publication_status: submitted
publisher: Research Square
status: public
title: WDFY3 cell autonomously controls neuronal migration
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11336'
abstract:
- lang: eng
text: The generation of a correctly-sized cerebral cortex with all-embracing neuronal
and glial cell-type diversity critically depends on faithful radial glial progenitor
(RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression
is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity
results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene
expression instructs RGP lineage progression is unknown. Here we utilize Mosaic
Analysis with Double Markers (MADM)-based single cell technology and demonstrate
that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts
at the global tissue-wide level. Conversely, cortical astrocyte production and
maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation.
We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression
that are dependent on complex interplays between intrinsic and tissue-wide properties.
In a broader context our results imply a critical role for the genetic and cellular
niche environment in neural stem cell behavior.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: LifeSc
acknowledgement: We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit) and S. Gharagozlou for technical support. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging & Optics
Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A.
received funding from the FWF Firnberg-Programm (T 1031). The work was supported by IST institutional funds and by the European Research Council (ERC) under the European Union’s Horizon
2020 research and innovation program (grant agreement 725780 LinPro) to S.H.
article_number: abq1263
article_processing_charge: No
article_type: original
author:
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular
landscape shapes the execution of sequential PRC2 functions in neural stem cell
lineage progression. Science Advances. 2022;8(44). doi:10.1126/sciadv.abq1263
apa: Amberg, N., Pauler, F., Streicher, C., & Hippenmeyer, S. (2022). Tissue-wide
genetic and cellular landscape shapes the execution of sequential PRC2 functions
in neural stem cell lineage progression. Science Advances. American Association
for the Advancement of Science. https://doi.org/10.1126/sciadv.abq1263
chicago: Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer.
“Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential
PRC2 Functions in Neural Stem Cell Lineage Progression.” Science Advances.
American Association for the Advancement of Science, 2022. https://doi.org/10.1126/sciadv.abq1263.
ieee: N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic
and cellular landscape shapes the execution of sequential PRC2 functions in neural
stem cell lineage progression,” Science Advances, vol. 8, no. 44. American
Association for the Advancement of Science, 2022.
ista: Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic
and cellular landscape shapes the execution of sequential PRC2 functions in neural
stem cell lineage progression. Science Advances. 8(44), abq1263.
mla: Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the
Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.”
Science Advances, vol. 8, no. 44, abq1263, American Association for the
Advancement of Science, 2022, doi:10.1126/sciadv.abq1263.
short: N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022).
corr_author: '1'
date_created: 2022-04-26T15:04:50Z
date_published: 2022-11-01T00:00:00Z
date_updated: 2025-09-09T14:30:38Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1126/sciadv.abq1263
ec_funded: 1
external_id:
isi:
- '000918406800019'
pmid:
- '36322669'
file:
- access_level: open_access
checksum: 0117023e188542082ca6693cf39e7f03
content_type: application/pdf
creator: patrickd
date_created: 2023-03-21T14:18:10Z
date_updated: 2023-03-21T14:18:10Z
file_id: '12742'
file_name: sciadv.abq1263.pdf
file_size: 2973998
relation: main_file
success: 1
file_date_updated: 2023-03-21T14:18:10Z
has_accepted_license: '1'
intvolume: ' 8'
isi: 1
issue: '44'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 268F8446-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: T01031
name: Role of Eed in neural stem cell lineage progression
publication: Science Advances
publication_identifier:
issn:
- 2375-2548
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
link:
- description: News on ISTA website
relation: press_release
url: https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/
scopus_import: '1'
status: public
title: Tissue-wide genetic and cellular landscape shapes the execution of sequential
PRC2 functions in neural stem cell lineage progression
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 8
year: '2022'
...
---
_id: '17067'
abstract:
- lang: eng
text: 'Human doublecortin (DCX) mutations are associated with severe brain malformations
leading to aberrant neuron positioning (heterotopia), intellectual disability
and epilepsy. DCX is a microtubule-associated protein which plays a key role during
neurodevelopment in neuronal migration and differentiation. Dcx knockout (KO)
mice show disorganized hippocampal pyramidal neurons. The CA2/CA3 pyramidal cell
layer is present as two abnormal layers and disorganized CA3 KO pyramidal neurons
are also more excitable than wild-type (WT) cells. To further identify abnormalities,
we characterized Dcx KO hippocampal neurons at subcellular, molecular and ultrastructural
levels. Severe defects were observed in mitochondria, affecting number and distribution.
Also, the Golgi apparatus was visibly abnormal, increased in volume and abnormally
organized. Transcriptome analyses from laser microdissected hippocampal tissue
at postnatal day 60 (P60) highlighted organelle abnormalities. Ultrastructural
studies of CA3 cells performed in P60 (young adult) and > 9 months (mature) tissue
showed that organelle defects are persistent throughout life. Locomotor activity
and fear memory of young and mature adults were also abnormal: Dcx KO mice consistently
performed less well than WT littermates, with defects becoming more severe with
age. Thus, we show that disruption of a neurodevelopmentally-regulated gene can
lead to permanent organelle anomalies contributing to abnormal adult behavior.'
acknowledgement: "We thank Sylvie Dumont for initial aid with laser microdissection
and G. Martinez-Lorenzana for experimental help with electron microscopy. We thank
the animal experimentation facility and cellular and tissue imaging platforms at
the Institut du Fer à Moulin, supported also by the Région Ile de France and the
FRC Rotary. The Francis lab was associated with the BioPsy Labex project and the
Ecole des Neurosciences de Paris Ile-de-France (ENP) network. Our salaries and lab
were supported by Inserm, the Centre national de la recherche scientifique (CNRS)
and Sorbonne University. The Francis group obtained the following funding contributing
to this project: the European Union (EU- HEALTH-2013, DESIRE, N° 60253), the JTC
2015 Neurodevelopmental Disorders affiliated with the French Agence National de
la Recherche (for \r\nNEURON8-Full- 815-006 STEM-MCD, to FF), E-Rare-3, the ERA-Net
for Research on Rare Diseases affiliated with the French ANR (ERARE18-049), the
European Cooperation on Science and Technology (COST Action CA16118)."
article_number: '105702'
article_processing_charge: Yes
article_type: original
author:
- first_name: Melissa A
full_name: Stouffer, Melissa A
id: 4C9372C4-F248-11E8-B48F-1D18A9856A87
last_name: Stouffer
- first_name: R.
full_name: Khalaf-Nazzal, R.
last_name: Khalaf-Nazzal
- first_name: C.
full_name: Cifuentes-Diaz, C.
last_name: Cifuentes-Diaz
- first_name: G.
full_name: Albertini, G.
last_name: Albertini
- first_name: E.
full_name: Bandet, E.
last_name: Bandet
- first_name: G.
full_name: Grannec, G.
last_name: Grannec
- first_name: V.
full_name: Lavilla, V.
last_name: Lavilla
- first_name: J.-F.
full_name: Deleuze, J.-F.
last_name: Deleuze
- first_name: R.
full_name: Olaso, R.
last_name: Olaso
- first_name: M.
full_name: Nosten-Bertrand, M.
last_name: Nosten-Bertrand
- first_name: F.
full_name: Francis, F.
last_name: Francis
citation:
ama: Stouffer MA, Khalaf-Nazzal R, Cifuentes-Diaz C, et al. Doublecortin mutation
leads to persistent defects in the Golgi apparatus and mitochondria in adult hippocampal
pyramidal cells. Neurobiology of Disease. 2022;168. doi:10.1016/j.nbd.2022.105702
apa: Stouffer, M. A., Khalaf-Nazzal, R., Cifuentes-Diaz, C., Albertini, G., Bandet,
E., Grannec, G., … Francis, F. (2022). Doublecortin mutation leads to persistent
defects in the Golgi apparatus and mitochondria in adult hippocampal pyramidal
cells. Neurobiology of Disease. Elsevier. https://doi.org/10.1016/j.nbd.2022.105702
chicago: Stouffer, Melissa A, R. Khalaf-Nazzal, C. Cifuentes-Diaz, G. Albertini,
E. Bandet, G. Grannec, V. Lavilla, et al. “Doublecortin Mutation Leads to Persistent
Defects in the Golgi Apparatus and Mitochondria in Adult Hippocampal Pyramidal
Cells.” Neurobiology of Disease. Elsevier, 2022. https://doi.org/10.1016/j.nbd.2022.105702.
ieee: M. A. Stouffer et al., “Doublecortin mutation leads to persistent defects
in the Golgi apparatus and mitochondria in adult hippocampal pyramidal cells,”
Neurobiology of Disease, vol. 168. Elsevier, 2022.
ista: Stouffer MA, Khalaf-Nazzal R, Cifuentes-Diaz C, Albertini G, Bandet E, Grannec
G, Lavilla V, Deleuze J-F, Olaso R, Nosten-Bertrand M, Francis F. 2022. Doublecortin
mutation leads to persistent defects in the Golgi apparatus and mitochondria in
adult hippocampal pyramidal cells. Neurobiology of Disease. 168, 105702.
mla: Stouffer, Melissa A., et al. “Doublecortin Mutation Leads to Persistent Defects
in the Golgi Apparatus and Mitochondria in Adult Hippocampal Pyramidal Cells.”
Neurobiology of Disease, vol. 168, 105702, Elsevier, 2022, doi:10.1016/j.nbd.2022.105702.
short: M.A. Stouffer, R. Khalaf-Nazzal, C. Cifuentes-Diaz, G. Albertini, E. Bandet,
G. Grannec, V. Lavilla, J.-F. Deleuze, R. Olaso, M. Nosten-Bertrand, F. Francis,
Neurobiology of Disease 168 (2022).
date_created: 2024-05-29T06:10:05Z
date_published: 2022-06-15T00:00:00Z
date_updated: 2024-08-06T06:57:39Z
day: '15'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.nbd.2022.105702
external_id:
pmid:
- '35339680'
file:
- access_level: open_access
checksum: b705d3d23d0b424ba29920be7ab64c23
content_type: application/pdf
creator: dernst
date_created: 2024-08-06T06:54:24Z
date_updated: 2024-08-06T06:54:24Z
file_id: '17398'
file_name: 2022_NeurobioDisease_Stouffer.pdf
file_size: 8890818
relation: main_file
success: 1
file_date_updated: 2024-08-06T06:54:24Z
has_accepted_license: '1'
intvolume: ' 168'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: Neurobiology of Disease
publication_identifier:
issn:
- 0969-9961
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Doublecortin mutation leads to persistent defects in the Golgi apparatus and
mitochondria in adult hippocampal pyramidal cells
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 168
year: '2022'
...
---
_id: '9794'
abstract:
- lang: eng
text: 'Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular
cells that form dedicated niches for immune cell interaction and capsular fibroblasts
that build a shell around the organ. Immunological challenge causes LNs to increase
more than tenfold in size within a few days. Here, we characterized the biomechanics
of LN swelling on the cellular and organ scale. We identified lymphocyte trapping
by influx and proliferation as drivers of an outward pressure force, causing fibroblastic
reticular cells of the T-zone (TRCs) and their associated conduits to stretch.
After an initial phase of relaxation, TRCs sensed the resulting strain through
cell matrix adhesions, which coordinated local growth and remodeling of the stromal
network. While the expanded TRC network readopted its typical configuration, a
massive fibrotic reaction of the organ capsule set in and countered further organ
expansion. Thus, different fibroblast populations mechanically control LN swelling
in a multitier fashion.'
acknowledged_ssus:
- _id: Bio
- _id: EM-Fac
- _id: PreCl
- _id: LifeSc
acknowledgement: This research was supported by the Scientific Service Units of IST
Austria through resources provided by the Imaging and Optics, Electron Microscopy,
Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd
antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing
a custom 3D channel alignment script. This work was supported by a European Research
Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR
20-24603Y and Charles University PRIMUS/20/MED/013.
article_processing_charge: No
article_type: original
author:
- first_name: Frank P
full_name: Assen, Frank P
id: 3A8E7F24-F248-11E8-B48F-1D18A9856A87
last_name: Assen
orcid: 0000-0003-3470-6119
- first_name: Jun
full_name: Abe, Jun
last_name: Abe
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Shayan
full_name: Shamipour, Shayan
id: 40B34FE2-F248-11E8-B48F-1D18A9856A87
last_name: Shamipour
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Tommaso
full_name: Costanzo, Tommaso
id: D93824F4-D9BA-11E9-BB12-F207E6697425
last_name: Costanzo
orcid: 0000-0001-9732-3815
- first_name: Gabriel
full_name: Krens, Gabriel
id: 2B819732-F248-11E8-B48F-1D18A9856A87
last_name: Krens
orcid: 0000-0003-4761-5996
- first_name: Markus
full_name: Brown, Markus
id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
last_name: Brown
- first_name: Burkhard
full_name: Ludewig, Burkhard
last_name: Ludewig
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Carl-Philipp J
full_name: Heisenberg, Carl-Philipp J
id: 39427864-F248-11E8-B48F-1D18A9856A87
last_name: Heisenberg
orcid: 0000-0002-0912-4566
- first_name: Wolfgang
full_name: Weninger, Wolfgang
last_name: Weninger
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Sanjiv A.
full_name: Luther, Sanjiv A.
last_name: Luther
- first_name: Jens V.
full_name: Stein, Jens V.
last_name: Stein
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-4561-241X
citation:
ama: Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations
in swelling lymph nodes. Nature Immunology. 2022;23:1246-1255. doi:10.1038/s41590-022-01257-4
apa: Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W.,
… Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling
lymph nodes. Nature Immunology. Springer Nature. https://doi.org/10.1038/s41590-022-01257-4
chicago: Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour,
Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal
Adaptations in Swelling Lymph Nodes.” Nature Immunology. Springer Nature,
2022. https://doi.org/10.1038/s41590-022-01257-4.
ieee: F. P. Assen et al., “Multitier mechanics control stromal adaptations
in swelling lymph nodes,” Nature Immunology, vol. 23. Springer Nature,
pp. 1246–1255, 2022.
ista: Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T,
Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo
EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations
in swelling lymph nodes. Nature Immunology. 23, 1246–1255.
mla: Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in
Swelling Lymph Nodes.” Nature Immunology, vol. 23, Springer Nature, 2022,
pp. 1246–55, doi:10.1038/s41590-022-01257-4.
short: F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T.
Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg,
W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology
23 (2022) 1246–1255.
corr_author: '1'
date_created: 2021-08-06T09:09:11Z
date_published: 2022-07-11T00:00:00Z
date_updated: 2025-06-11T13:52:43Z
day: '11'
ddc:
- '570'
department:
- _id: SiHi
- _id: CaHe
- _id: EdHa
- _id: EM-Fac
- _id: Bio
- _id: MiSi
doi: 10.1038/s41590-022-01257-4
ec_funded: 1
external_id:
isi:
- '000822975900002'
pmid:
- '35817845'
file:
- access_level: open_access
checksum: 628e7b49809f22c75b428842efe70c68
content_type: application/pdf
creator: dernst
date_created: 2022-07-25T07:11:32Z
date_updated: 2022-07-25T07:11:32Z
file_id: '11642'
file_name: 2022_NatureImmunology_Assen.pdf
file_size: 11475325
relation: main_file
success: 1
file_date_updated: 2022-07-25T07:11:32Z
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1246-1255
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular Navigation Along Spatial Gradients
publication: Nature Immunology
publication_identifier:
eissn:
- 1529-2916
issn:
- 1529-2908
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Multitier mechanics control stromal adaptations in swelling lymph nodes
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2022'
...
---
_id: '10764'
abstract:
- lang: eng
text: Presynaptic glutamate replenishment is fundamental to brain function. In high
activity regimes, such as epileptic episodes, this process is thought to rely
on the glutamate-glutamine cycle between neurons and astrocytes. However the presence
of an astroglial glutamine supply, as well as its functional relevance in vivo
in the healthy brain remain controversial, partly due to a lack of tools that
can directly examine glutamine transfer. Here, we generated a fluorescent probe
that tracks glutamine in live cells, which provides direct visual evidence of
an activity-dependent glutamine supply from astroglial networks to presynaptic
structures under physiological conditions. This mobilization is mediated by connexin43,
an astroglial protein with both gap-junction and hemichannel functions, and is
essential for synaptic transmission and object recognition memory. Our findings
uncover an indispensable recruitment of astroglial glutamine in physiological
synaptic activity and memory via an unconventional pathway, thus providing an
astrocyte basis for cognitive processes.
acknowledgement: 'We thank D. Mazaud and. J. Cazères for technical assistance. This
work was supported by grants from the European Research Council (Consolidator grant
#683154) and European Union’s Horizon 2020 research and innovation program (Marie
Sklodowska-Curie Innovative Training Networks, grant #722053, EU-GliaPhD) to N.R.
and from FP7-PEOPLE Marie Curie Intra-European Fellowship for career development
(grant #622289) to G.C.'
article_number: '753'
article_processing_charge: No
article_type: original
author:
- first_name: Giselle T
full_name: Cheung, Giselle T
id: 471195F6-F248-11E8-B48F-1D18A9856A87
last_name: Cheung
orcid: 0000-0001-8457-2572
- first_name: Danijela
full_name: Bataveljic, Danijela
last_name: Bataveljic
- first_name: Josien
full_name: Visser, Josien
last_name: Visser
- first_name: Naresh
full_name: Kumar, Naresh
last_name: Kumar
- first_name: Julien
full_name: Moulard, Julien
last_name: Moulard
- first_name: Glenn
full_name: Dallérac, Glenn
last_name: Dallérac
- first_name: Daria
full_name: Mozheiko, Daria
last_name: Mozheiko
- first_name: Astrid
full_name: Rollenhagen, Astrid
last_name: Rollenhagen
- first_name: Pascal
full_name: Ezan, Pascal
last_name: Ezan
- first_name: Cédric
full_name: Mongin, Cédric
last_name: Mongin
- first_name: Oana
full_name: Chever, Oana
last_name: Chever
- first_name: Alexis Pierre
full_name: Bemelmans, Alexis Pierre
last_name: Bemelmans
- first_name: Joachim
full_name: Lübke, Joachim
last_name: Lübke
- first_name: Isabelle
full_name: Leray, Isabelle
last_name: Leray
- first_name: Nathalie
full_name: Rouach, Nathalie
last_name: Rouach
citation:
ama: Cheung GT, Bataveljic D, Visser J, et al. Physiological synaptic activity and
recognition memory require astroglial glutamine. Nature Communications.
2022;13. doi:10.1038/s41467-022-28331-7
apa: Cheung, G. T., Bataveljic, D., Visser, J., Kumar, N., Moulard, J., Dallérac,
G., … Rouach, N. (2022). Physiological synaptic activity and recognition memory
require astroglial glutamine. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-28331-7
chicago: Cheung, Giselle T, Danijela Bataveljic, Josien Visser, Naresh Kumar, Julien
Moulard, Glenn Dallérac, Daria Mozheiko, et al. “Physiological Synaptic Activity
and Recognition Memory Require Astroglial Glutamine.” Nature Communications.
Springer Nature, 2022. https://doi.org/10.1038/s41467-022-28331-7.
ieee: G. T. Cheung et al., “Physiological synaptic activity and recognition
memory require astroglial glutamine,” Nature Communications, vol. 13. Springer
Nature, 2022.
ista: Cheung GT, Bataveljic D, Visser J, Kumar N, Moulard J, Dallérac G, Mozheiko
D, Rollenhagen A, Ezan P, Mongin C, Chever O, Bemelmans AP, Lübke J, Leray I,
Rouach N. 2022. Physiological synaptic activity and recognition memory require
astroglial glutamine. Nature Communications. 13, 753.
mla: Cheung, Giselle T., et al. “Physiological Synaptic Activity and Recognition
Memory Require Astroglial Glutamine.” Nature Communications, vol. 13, 753,
Springer Nature, 2022, doi:10.1038/s41467-022-28331-7.
short: G.T. Cheung, D. Bataveljic, J. Visser, N. Kumar, J. Moulard, G. Dallérac,
D. Mozheiko, A. Rollenhagen, P. Ezan, C. Mongin, O. Chever, A.P. Bemelmans, J.
Lübke, I. Leray, N. Rouach, Nature Communications 13 (2022).
date_created: 2022-02-20T23:01:30Z
date_published: 2022-02-08T00:00:00Z
date_updated: 2026-04-02T12:22:38Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41467-022-28331-7
external_id:
isi:
- '000757297200017'
pmid:
- '35136061'
file:
- access_level: open_access
checksum: 51d580aff2327dd957946208a9749e1a
content_type: application/pdf
creator: dernst
date_created: 2022-02-21T07:51:33Z
date_updated: 2022-02-21T07:51:33Z
file_id: '10777'
file_name: 2022_NatureCommunications_Cheung.pdf
file_size: 7910519
relation: main_file
success: 1
file_date_updated: 2022-02-21T07:51:33Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Physiological synaptic activity and recognition memory require astroglial glutamine
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 13
year: '2022'
...
---
_id: '10791'
abstract:
- lang: eng
text: The mammalian neocortex is composed of diverse neuronal and glial cell classes
that broadly arrange in six distinct laminae. Cortical layers emerge during development
and defects in the developmental programs that orchestrate cortical lamination
are associated with neurodevelopmental diseases. The developmental principle of
cortical layer formation depends on concerted radial projection neuron migration,
from their birthplace to their final target position. Radial migration occurs
in defined sequential steps, regulated by a large array of signaling pathways.
However, based on genetic loss-of-function experiments, most studies have thus
far focused on the role of cell-autonomous gene function. Yet, cortical neuron
migration in situ is a complex process and migrating neurons traverse along diverse
cellular compartments and environments. The role of tissue-wide properties and
genetic state in radial neuron migration is however not clear. Here we utilized
mosaic analysis with double markers (MADM) technology to either sparsely or globally
delete gene function, followed by quantitative single-cell phenotyping. The MADM-based
gene ablation paradigms in combination with computational modeling demonstrated
that global tissue-wide effects predominate cell-autonomous gene function albeit
in a gene-specific manner. Our results thus suggest that the genetic landscape
in a tissue critically affects the overall migration phenotype of individual cortical
projection neurons. In a broader context, our findings imply that global tissue-wide
effects represent an essential component of the underlying etiology associated
with focal malformations of cortical development in particular, and neurological
diseases in general.
acknowledged_ssus:
- _id: LifeSc
- _id: PreCl
- _id: Bio
acknowledgement: "A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian
Academy of Sciences. This work also received support from IST Austria institutional
funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh
Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC
funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and
C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical
support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer
lab for discussion. This research was supported by the Scientific Service Units
of IST Austria through resources provided by the Imaging and Optics Facility, Lab
Support Facility and Preclinical Facility."
article_number: kvac009
article_processing_charge: No
article_type: original
author:
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Björn
full_name: Hof, Björn
id: 3A374330-F248-11E8-B48F-1D18A9856A87
last_name: Hof
orcid: 0000-0003-2057-2754
- first_name: Li Huei
full_name: Tsai, Li Huei
last_name: Tsai
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic
gene function in radial neuron migration. Oxford Open Neuroscience. 2022;1(1).
doi:10.1093/oons/kvac009
apa: Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter,
S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene
function in radial neuron migration. Oxford Open Neuroscience. Oxford University
Press. https://doi.org/10.1093/oons/kvac009
chicago: Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena
Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override
Cell-Intrinsic Gene Function in Radial Neuron Migration.” Oxford Open Neuroscience.
Oxford University Press, 2022. https://doi.org/10.1093/oons/kvac009.
ieee: A. H. Hansen et al., “Tissue-wide effects override cell-intrinsic gene
function in radial neuron migration,” Oxford Open Neuroscience, vol. 1,
no. 1. Oxford University Press, 2022.
ista: Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM,
Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects
override cell-intrinsic gene function in radial neuron migration. Oxford Open
Neuroscience. 1(1), kvac009.
mla: Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function
in Radial Neuron Migration.” Oxford Open Neuroscience, vol. 1, no. 1, kvac009,
Oxford University Press, 2022, doi:10.1093/oons/kvac009.
short: A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter,
C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford
Open Neuroscience 1 (2022).
corr_author: '1'
date_created: 2022-02-25T07:52:11Z
date_published: 2022-07-07T00:00:00Z
date_updated: 2026-04-07T13:29:13Z
day: '07'
ddc:
- '570'
department:
- _id: SiHi
- _id: BjHo
- _id: LifeSc
- _id: EM-Fac
doi: 10.1093/oons/kvac009
ec_funded: 1
external_id:
pmid:
- '38596707'
file:
- access_level: open_access
checksum: 822e76e056c07099d1fb27d1ece5941b
content_type: application/pdf
creator: dernst
date_created: 2023-08-16T08:00:30Z
date_updated: 2023-08-16T08:00:30Z
file_id: '14061'
file_name: 2023_OxfordOpenNeuroscience_Hansen.pdf
file_size: 4846551
relation: main_file
success: 1
file_date_updated: 2023-08-16T08:00:30Z
has_accepted_license: '1'
intvolume: ' 1'
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular mechanisms of radial neuronal migration
publication: Oxford Open Neuroscience
publication_identifier:
eissn:
- 2753-149X
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
related_material:
record:
- id: '12726'
relation: dissertation_contains
status: public
- id: '14530'
relation: dissertation_contains
status: public
status: public
title: Tissue-wide effects override cell-intrinsic gene function in radial neuron
migration
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 1
year: '2022'
...
---
_id: '10655'
abstract:
- lang: eng
text: "Adeno-associated viruses (AAVs) are widely used to deliver genetic material
in vivo to distinct cell types such as neurons or glial cells, allowing for targeted
manipulation. Transduction of microglia is mostly excluded from this strategy,
likely due to the cells’ heterogeneous state upon environmental changes, which
makes AAV design challenging. Here, we established the retina as a model system
for microglial AAV validation and optimization. First, we show that AAV2/6 transduced
microglia in both synaptic layers, where layer preference corresponds to the intravitreal
or subretinal delivery method. Surprisingly, we observed significantly enhanced
microglial transduction during photoreceptor degeneration. Thus, we modified the
AAV6 capsid to reduce heparin binding by introducing four point mutations (K531E,
R576Q, K493S, and K459S), resulting in increased microglial transduction in the
outer plexiform layer. Finally, to improve microglial-specific transduction, we
validated a Cre-dependent transgene delivery cassette for use in combination with
the Cx3cr1CreERT2 mouse line. Together, our results provide a foundation for future
studies optimizing AAV-mediated microglia transduction and highlight that environmental
conditions influence microglial transduction efficiency.\r\n"
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement no. 715571). The research was supported by the Scientific Service
Units (SSU) of IST Austria through resources provided by the Bioimaging Facility,
the Life Science Facility, and the Pre-Clinical Facility, namely Sonja Haslinger
and Michael Schunn for their animal colony management and support. We would also
like to thank Chakrabarty Lab for sharing the plasmids for AAV2/6 production. Finally,
we would like to thank the Siegert team members for discussion about the manuscript.
article_processing_charge: Yes
article_type: original
author:
- first_name: Margaret E
full_name: Maes, Margaret E
id: 3838F452-F248-11E8-B48F-1D18A9856A87
last_name: Maes
orcid: 0000-0001-9642-1085
- first_name: Gabriele M.
full_name: Wögenstein, Gabriele M.
last_name: Wögenstein
- first_name: Gloria
full_name: Colombo, Gloria
id: 3483CF6C-F248-11E8-B48F-1D18A9856A87
last_name: Colombo
orcid: 0000-0001-9434-8902
- first_name: Raquel
full_name: Casado Polanco, Raquel
id: 15240fc1-dbcd-11ea-9d1d-ac5a786425fd
last_name: Casado Polanco
orcid: 0000-0001-8293-4568
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
citation:
ama: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
2021;23:210-224. doi:10.1016/j.omtm.2021.09.006
apa: Maes, M. E., Wögenstein, G. M., Colombo, G., Casado Polanco, R., & Siegert,
S. (2021). Optimizing AAV2/6 microglial targeting identified enhanced efficiency
in the photoreceptor degenerative environment. Molecular Therapy - Methods
and Clinical Development. Elsevier. https://doi.org/10.1016/j.omtm.2021.09.006
chicago: Maes, Margaret E, Gabriele M. Wögenstein, Gloria Colombo, Raquel Casado
Polanco, and Sandra Siegert. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development. Elsevier, 2021. https://doi.org/10.1016/j.omtm.2021.09.006.
ieee: M. E. Maes, G. M. Wögenstein, G. Colombo, R. Casado Polanco, and S. Siegert,
“Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment,” Molecular Therapy - Methods and Clinical
Development, vol. 23. Elsevier, pp. 210–224, 2021.
ista: Maes ME, Wögenstein GM, Colombo G, Casado Polanco R, Siegert S. 2021. Optimizing
AAV2/6 microglial targeting identified enhanced efficiency in the photoreceptor
degenerative environment. Molecular Therapy - Methods and Clinical Development.
23, 210–224.
mla: Maes, Margaret E., et al. “Optimizing AAV2/6 Microglial Targeting Identified
Enhanced Efficiency in the Photoreceptor Degenerative Environment.” Molecular
Therapy - Methods and Clinical Development, vol. 23, Elsevier, 2021, pp. 210–24,
doi:10.1016/j.omtm.2021.09.006.
short: M.E. Maes, G.M. Wögenstein, G. Colombo, R. Casado Polanco, S. Siegert, Molecular
Therapy - Methods and Clinical Development 23 (2021) 210–224.
corr_author: '1'
date_created: 2022-01-23T23:01:28Z
date_published: 2021-12-10T00:00:00Z
date_updated: 2025-04-14T07:41:46Z
day: '10'
ddc:
- '570'
department:
- _id: SaSi
- _id: SiHi
doi: 10.1016/j.omtm.2021.09.006
ec_funded: 1
external_id:
isi:
- '000748748500019'
file:
- access_level: open_access
checksum: 77dc540e8011c5475031bdf6ccef20a6
content_type: application/pdf
creator: cchlebak
date_created: 2022-01-24T07:43:09Z
date_updated: 2022-01-24T07:43:09Z
file_id: '10657'
file_name: 2021_MolTherMethodsClinDev_Maes.pdf
file_size: 4794147
relation: main_file
success: 1
file_date_updated: 2022-01-24T07:43:09Z
has_accepted_license: '1'
intvolume: ' 23'
isi: 1
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 210-224
project:
- _id: 25D4A630-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715571'
name: Microglia action towards neuronal circuit formation and function in health
and disease
publication: Molecular Therapy - Methods and Clinical Development
publication_identifier:
eissn:
- 2329-0501
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optimizing AAV2/6 microglial targeting identified enhanced efficiency in the
photoreceptor degenerative environment
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 23
year: '2021'
...
---
_id: '8544'
abstract:
- lang: eng
text: The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic
branches, yet this hypothesis has not been causally tested in vivo in the mammalian
brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2
mediate synaptogenesis between granule cells and Purkinje cells in the molecular
layer of the cerebellar cortex. Here we show that sparse but not global knockout
of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular
layer and overelaboration in the superficial molecular layer. Developmental, overexpression,
structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis
defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner.
A generative model of dendritic growth based on competitive synaptogenesis largely
recapitulates GluD2 sparse and global knockout phenotypes. Our results support
the synaptotrophic hypothesis at initial stages of dendrite development, suggest
a second mode in which cumulative synapse formation inhibits further dendrite
growth, and highlight the importance of competition in dendrite morphogenesis.
acknowledgement: We thank M. Mishina for GluD2fl frozen embryos, T.C. Südhof and J.I.
Morgan for Cbln1fl mice, L. Anderson for help in generating the MADM alleles, W.
Joo for a previously unpublished construct, M. Yuzaki, K. Shen, J. Ding, and members
of the Luo lab, including J.M. Kebschull, H. Li, J. Li, T. Li, C.M. McLaughlin,
D. Pederick, J. Ren, D.C. Wang and C. Xu for discussions and critiques of the manuscript,
and M. Yuzaki for supporting Y.H.T. during the final phase of this project. Y.H.T.
was supported by a JSPS fellowship; S.A.S. was supported by a Stanford Graduate
Fellowship and an NSF Predoctoral Fellowship; L.J. is supported by a Stanford Graduate
Fellowship and an NSF Predoctoral Fellowship; M.J.W. is supported by a Burroughs
Wellcome Fund CASI Award. This work was supported by an NIH grant (R01-NS050538)
to L.L.; the European Research Council (ERC) under the European Union's Horizon
2020 research and innovations programme (No. 725780 LinPro) to S.H.; and Simons
and James S. McDonnell Foundations and an NSF CAREER award to S.G.; L.L. is an HHMI
investigator.
article_processing_charge: No
article_type: original
author:
- first_name: Yukari H.
full_name: Takeo, Yukari H.
last_name: Takeo
- first_name: S. Andrew
full_name: Shuster, S. Andrew
last_name: Shuster
- first_name: Linnie
full_name: Jiang, Linnie
last_name: Jiang
- first_name: Miley
full_name: Hu, Miley
last_name: Hu
- first_name: David J.
full_name: Luginbuhl, David J.
last_name: Luginbuhl
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Mark J.
full_name: Wagner, Mark J.
last_name: Wagner
- first_name: Surya
full_name: Ganguli, Surya
last_name: Ganguli
- first_name: Liqun
full_name: Luo, Liqun
last_name: Luo
citation:
ama: Takeo YH, Shuster SA, Jiang L, et al. GluD2- and Cbln1-mediated competitive
synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. Neuron.
2021;109(4):P629-644.E8. doi:10.1016/j.neuron.2020.11.028
apa: Takeo, Y. H., Shuster, S. A., Jiang, L., Hu, M., Luginbuhl, D. J., Rülicke,
T., … Luo, L. (2021). GluD2- and Cbln1-mediated competitive synaptogenesis shapes
the dendritic arbors of cerebellar Purkinje cells. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2020.11.028
chicago: Takeo, Yukari H., S. Andrew Shuster, Linnie Jiang, Miley Hu, David J. Luginbuhl,
Thomas Rülicke, Ximena Contreras, et al. “GluD2- and Cbln1-Mediated Competitive
Synaptogenesis Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” Neuron.
Elsevier, 2021. https://doi.org/10.1016/j.neuron.2020.11.028.
ieee: Y. H. Takeo et al., “GluD2- and Cbln1-mediated competitive synaptogenesis
shapes the dendritic arbors of cerebellar Purkinje cells,” Neuron, vol.
109, no. 4. Elsevier, p. P629–644.E8, 2021.
ista: Takeo YH, Shuster SA, Jiang L, Hu M, Luginbuhl DJ, Rülicke T, Contreras X,
Hippenmeyer S, Wagner MJ, Ganguli S, Luo L. 2021. GluD2- and Cbln1-mediated competitive
synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells. Neuron.
109(4), P629–644.E8.
mla: Takeo, Yukari H., et al. “GluD2- and Cbln1-Mediated Competitive Synaptogenesis
Shapes the Dendritic Arbors of Cerebellar Purkinje Cells.” Neuron, vol.
109, no. 4, Elsevier, 2021, p. P629–644.E8, doi:10.1016/j.neuron.2020.11.028.
short: Y.H. Takeo, S.A. Shuster, L. Jiang, M. Hu, D.J. Luginbuhl, T. Rülicke, X.
Contreras, S. Hippenmeyer, M.J. Wagner, S. Ganguli, L. Luo, Neuron 109 (2021)
P629–644.E8.
date_created: 2020-09-21T11:59:47Z
date_published: 2021-02-17T00:00:00Z
date_updated: 2025-09-10T09:58:28Z
day: '17'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2020.11.028
ec_funded: 1
external_id:
isi:
- '000632657400006'
pmid:
- '33352118'
intvolume: ' 109'
isi: 1
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.06.14.151258
month: '02'
oa: 1
oa_version: Preprint
page: P629-644.E8
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Neuron
publication_identifier:
eissn:
- 1097-4199
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors
of cerebellar Purkinje cells
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 109
year: '2021'
...
---
_id: '9082'
abstract:
- lang: eng
text: Acquired mutations are sufficiently frequent such that the genome of a single
cell offers a record of its history of cell divisions. Among more common somatic
genomic alterations are loss of heterozygosity (LOH). Large LOH events are potentially
detectable in single cell RNA sequencing (scRNA-seq) datasets as tracts of monoallelic
expression for constitutionally heterozygous single nucleotide variants (SNVs)
located among contiguous genes. We identified runs of monoallelic expression,
consistent with LOH, uniquely distributed throughout the genome in single cell
brain cortex transcriptomes of F1 hybrids involving different inbred mouse strains.
We then phylogenetically reconstructed single cell lineages and simultaneously
identified cell types by corresponding gene expression patterns. Our results are
consistent with progenitor cells giving rise to multiple cortical cell types through
stereotyped expansion and distinct waves of neurogenesis. Compared to engineered
recording systems, LOH events accumulate throughout the genome and across the
lifetime of an organism, affording tremendous capacity for encoding lineage information
and increasing resolution for later cell divisions. This approach can conceivably
be computationally incorporated into scRNA-seq analysis and may be useful for
organisms where genetic engineering is prohibitive, such as humans.
acknowledgement: "We thank Bill Bolosky, Microsoft Research, for earlier work showing
proof of concept in TCGA\r\nbulk RNA-seq data. Supported by the Paul G. Allen Frontiers
Group (University of Washington);\r\nNIH R00HG010152 (Dartmouth); and NÖ Forschung
und Bildung n[f+b] life science call grant\r\n(C13-002) to SH, and the European
Research Council (ERC) under the European Union’s\r\nHorizon 2020 research and innovation
program 725780 LinPro to SH."
article_processing_charge: No
author:
- first_name: Donovan J.
full_name: Anderson, Donovan J.
last_name: Anderson
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Aaron
full_name: McKenna, Aaron
last_name: McKenna
- first_name: Jay
full_name: Shendure, Jay
last_name: Shendure
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Marshall S.
full_name: Horwitz, Marshall S.
last_name: Horwitz
citation:
ama: Anderson DJ, Pauler F, McKenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous
identification of brain cell type and lineage via single cell RNA sequencing.
bioRxiv. doi:10.1101/2020.12.31.425016
apa: Anderson, D. J., Pauler, F., McKenna, A., Shendure, J., Hippenmeyer, S., &
Horwitz, M. S. (n.d.). Simultaneous identification of brain cell type and lineage
via single cell RNA sequencing. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2020.12.31.425016
chicago: Anderson, Donovan J., Florian Pauler, Aaron McKenna, Jay Shendure, Simon
Hippenmeyer, and Marshall S. Horwitz. “Simultaneous Identification of Brain Cell
Type and Lineage via Single Cell RNA Sequencing.” BioRxiv. Cold Spring
Harbor Laboratory, n.d. https://doi.org/10.1101/2020.12.31.425016.
ieee: D. J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, and M.
S. Horwitz, “Simultaneous identification of brain cell type and lineage via single
cell RNA sequencing,” bioRxiv. Cold Spring Harbor Laboratory.
ista: Anderson DJ, Pauler F, McKenna A, Shendure J, Hippenmeyer S, Horwitz MS. Simultaneous
identification of brain cell type and lineage via single cell RNA sequencing.
bioRxiv, 10.1101/2020.12.31.425016.
mla: Anderson, Donovan J., et al. “Simultaneous Identification of Brain Cell Type
and Lineage via Single Cell RNA Sequencing.” BioRxiv, Cold Spring Harbor
Laboratory, doi:10.1101/2020.12.31.425016.
short: D.J. Anderson, F. Pauler, A. McKenna, J. Shendure, S. Hippenmeyer, M.S. Horwitz,
BioRxiv (n.d.).
date_created: 2021-02-04T07:23:23Z
date_published: 2021-01-01T00:00:00Z
date_updated: 2025-04-14T07:43:04Z
day: '01'
department:
- _id: SiHi
doi: 10.1101/2020.12.31.425016
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.12.31.425016
month: '01'
oa: 1
oa_version: Preprint
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: bioRxiv
publication_status: submitted
publisher: Cold Spring Harbor Laboratory
status: public
title: Simultaneous identification of brain cell type and lineage via single cell
RNA sequencing
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2021'
...
---
_id: '9188'
abstract:
- lang: eng
text: Genomic imprinting is an epigenetic mechanism that results in parental allele-specific
expression of ~1% of all genes in mouse and human. Imprinted genes are key developmental
regulators and play pivotal roles in many biological processes such as nutrient
transfer from the mother to offspring and neuronal development. Imprinted genes
are also involved in human disease, including neurodevelopmental disorders, and
often occur in clusters that are regulated by a common imprint control region
(ICR). In extra-embryonic tissues ICRs can act over large distances, with the
largest surrounding Igf2r spanning over 10 million base-pairs. Besides classical
imprinted expression that shows near exclusive maternal or paternal expression,
widespread biased imprinted expression has been identified mainly in brain. In
this review we discuss recent developments mapping cell type specific imprinted
expression in extra-embryonic tissues and neocortex in the mouse. We highlight
the advantages of using an inducible uniparental chromosome disomy (UPD) system
to generate cells carrying either two maternal or two paternal copies of a specific
chromosome to analyze the functional consequences of genomic imprinting. Mosaic
Analysis with Double Markers (MADM) allows fluorescent labeling and concomitant
induction of UPD sparsely in specific cell types, and thus to over-express or
suppress all imprinted genes on that chromosome. To illustrate the utility of
this technique, we explain how MADM-induced UPD revealed new insights about the
function of the well-studied Cdkn1c imprinted gene, and how MADM-induced UPDs
led to identification of highly cell type specific phenotypes related to perturbed
imprinted expression in the mouse neocortex. Finally, we give an outlook on how
MADM could be used to probe cell type specific imprinted expression in other tissues
in mouse, particularly in extra-embryonic tissues.
acknowledgement: We thank Melissa Stouffer for critically reading the manuscript.
This work was supported by IST Austria institutional funds; NÖ Forschung und Bildung
n[f + b] life science call grant (C13-002) to S.H. and the European Research Council
(ERC) under the European Union's Horizon 2020 research and innovation program (grant
agreement 725780 LinPro) to S.H.
article_number: '104986'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Quanah
full_name: Hudson, Quanah
last_name: Hudson
- first_name: Susanne
full_name: Laukoter, Susanne
id: 2D6B7A9A-F248-11E8-B48F-1D18A9856A87
last_name: Laukoter
orcid: 0000-0002-7903-3010
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. Inducible uniparental chromosome
disomy to probe genomic imprinting at single-cell level in brain and beyond. Neurochemistry
International. 2021;145(5). doi:10.1016/j.neuint.2021.104986
apa: Pauler, F., Hudson, Q., Laukoter, S., & Hippenmeyer, S. (2021). Inducible
uniparental chromosome disomy to probe genomic imprinting at single-cell level
in brain and beyond. Neurochemistry International. Elsevier. https://doi.org/10.1016/j.neuint.2021.104986
chicago: Pauler, Florian, Quanah Hudson, Susanne Laukoter, and Simon Hippenmeyer.
“Inducible Uniparental Chromosome Disomy to Probe Genomic Imprinting at Single-Cell
Level in Brain and Beyond.” Neurochemistry International. Elsevier, 2021.
https://doi.org/10.1016/j.neuint.2021.104986.
ieee: F. Pauler, Q. Hudson, S. Laukoter, and S. Hippenmeyer, “Inducible uniparental
chromosome disomy to probe genomic imprinting at single-cell level in brain and
beyond,” Neurochemistry International, vol. 145, no. 5. Elsevier, 2021.
ista: Pauler F, Hudson Q, Laukoter S, Hippenmeyer S. 2021. Inducible uniparental
chromosome disomy to probe genomic imprinting at single-cell level in brain and
beyond. Neurochemistry International. 145(5), 104986.
mla: Pauler, Florian, et al. “Inducible Uniparental Chromosome Disomy to Probe Genomic
Imprinting at Single-Cell Level in Brain and Beyond.” Neurochemistry International,
vol. 145, no. 5, 104986, Elsevier, 2021, doi:10.1016/j.neuint.2021.104986.
short: F. Pauler, Q. Hudson, S. Laukoter, S. Hippenmeyer, Neurochemistry International
145 (2021).
date_created: 2021-02-23T12:31:43Z
date_published: 2021-05-01T00:00:00Z
date_updated: 2025-04-14T07:43:04Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.neuint.2021.104986
ec_funded: 1
external_id:
isi:
- '000635575000005'
pmid:
- '33600873'
file:
- access_level: open_access
checksum: c6d7a40089cd29e289f9b22e75768304
content_type: application/pdf
creator: kschuh
date_created: 2021-08-11T12:30:38Z
date_updated: 2021-08-11T12:30:38Z
file_id: '9883'
file_name: 2021_NCI_Pauler.pdf
file_size: 7083499
relation: main_file
success: 1
file_date_updated: 2021-08-11T12:30:38Z
has_accepted_license: '1'
intvolume: ' 145'
isi: 1
issue: '5'
keyword:
- Cell Biology
- Cellular and Molecular Neuroscience
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 25D92700-B435-11E9-9278-68D0E5697425
grant_number: LS13-002
name: Mapping Cell-Type Specificity of the Genomic Imprintome in the Brain
publication: Neurochemistry International
publication_identifier:
issn:
- 0197-0186
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell
level in brain and beyond
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 145
year: '2021'
...
---
_id: '9793'
abstract:
- lang: eng
text: Astrocytes extensively infiltrate the neuropil to regulate critical aspects
of synaptic development and function. This process is regulated by transcellular
interactions between astrocytes and neurons via cell adhesion molecules. How astrocytes
coordinate developmental processes among one another to parse out the synaptic
neuropil and form non-overlapping territories is unknown. Here we identify a molecular
mechanism regulating astrocyte-astrocyte interactions during development to coordinate
astrocyte morphogenesis and gap junction coupling. We show that hepaCAM, a disease-linked,
astrocyte-enriched cell adhesion molecule, regulates astrocyte competition for
territory and morphological complexity in the developing mouse cortex. Furthermore,
conditional deletion of Hepacam from developing astrocytes significantly impairs
gap junction coupling between astrocytes and disrupts the balance between synaptic
excitation and inhibition. Mutations in HEPACAM cause megalencephalic leukoencephalopathy
with subcortical cysts in humans. Therefore, our findings suggest that disruption
of astrocyte self-organization mechanisms could be an underlying cause of neural
pathology.
acknowledgement: This work was supported by the National Institutes of Health (R01
DA047258 and R01 NS102237 to C.E., F32 NS100392 to K.T.B.) and the Holland-Trice
Brain Research Award (to C.E.). K.T.B. was supported by postdoctoral fellowships
from the Foerster-Bernstein Family and The Hartwell Foundation. The Hippenmeyer
lab was supported by the European Research Council (ERC) under the European Union’s
Horizon 2020 research and innovations program (725780 LinPro) to S.H. R.E. was supported
by Ministerio de Ciencia y Tecnología (RTI2018-093493-B-I00). We thank the Duke
Light Microscopy Core Facility, the Duke Transgenic Mouse Facility, Dr. U. Schulte
for assistance with proteomic experiments, and Dr. D. Silver for critical review
of the manuscript. Cartoon elements of figure panels were created using BioRender.com.
article_processing_charge: No
article_type: original
author:
- first_name: Katherine T.
full_name: Baldwin, Katherine T.
last_name: Baldwin
- first_name: Christabel X.
full_name: Tan, Christabel X.
last_name: Tan
- first_name: Samuel T.
full_name: Strader, Samuel T.
last_name: Strader
- first_name: Changyu
full_name: Jiang, Changyu
last_name: Jiang
- first_name: Justin T.
full_name: Savage, Justin T.
last_name: Savage
- first_name: Xabier
full_name: Elorza-Vidal, Xabier
last_name: Elorza-Vidal
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Thomas
full_name: Rülicke, Thomas
last_name: Rülicke
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Raúl
full_name: Estévez, Raúl
last_name: Estévez
- first_name: Ru-Rong
full_name: Ji, Ru-Rong
last_name: Ji
- first_name: Cagla
full_name: Eroglu, Cagla
last_name: Eroglu
citation:
ama: Baldwin KT, Tan CX, Strader ST, et al. HepaCAM controls astrocyte self-organization
and coupling. Neuron. 2021;109(15):2427-2442.e10. doi:10.1016/j.neuron.2021.05.025
apa: Baldwin, K. T., Tan, C. X., Strader, S. T., Jiang, C., Savage, J. T., Elorza-Vidal,
X., … Eroglu, C. (2021). HepaCAM controls astrocyte self-organization and coupling.
Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2021.05.025
chicago: Baldwin, Katherine T., Christabel X. Tan, Samuel T. Strader, Changyu Jiang,
Justin T. Savage, Xabier Elorza-Vidal, Ximena Contreras, et al. “HepaCAM Controls
Astrocyte Self-Organization and Coupling.” Neuron. Elsevier, 2021. https://doi.org/10.1016/j.neuron.2021.05.025.
ieee: K. T. Baldwin et al., “HepaCAM controls astrocyte self-organization
and coupling,” Neuron, vol. 109, no. 15. Elsevier, p. 2427–2442.e10, 2021.
ista: Baldwin KT, Tan CX, Strader ST, Jiang C, Savage JT, Elorza-Vidal X, Contreras
X, Rülicke T, Hippenmeyer S, Estévez R, Ji R-R, Eroglu C. 2021. HepaCAM controls
astrocyte self-organization and coupling. Neuron. 109(15), 2427–2442.e10.
mla: Baldwin, Katherine T., et al. “HepaCAM Controls Astrocyte Self-Organization
and Coupling.” Neuron, vol. 109, no. 15, Elsevier, 2021, p. 2427–2442.e10,
doi:10.1016/j.neuron.2021.05.025.
short: K.T. Baldwin, C.X. Tan, S.T. Strader, C. Jiang, J.T. Savage, X. Elorza-Vidal,
X. Contreras, T. Rülicke, S. Hippenmeyer, R. Estévez, R.-R. Ji, C. Eroglu, Neuron
109 (2021) 2427–2442.e10.
date_created: 2021-08-06T09:08:25Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2025-04-14T07:43:03Z
day: '04'
department:
- _id: SiHi
doi: 10.1016/j.neuron.2021.05.025
ec_funded: 1
external_id:
isi:
- '000692851900010'
pmid:
- '34171291'
intvolume: ' 109'
isi: 1
issue: '15'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.neuron.2021.05.025
month: '08'
oa: 1
oa_version: Published Version
page: 2427-2442.e10
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
publication: Neuron
publication_identifier:
eissn:
- 1097-4199
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: HepaCAM controls astrocyte self-organization and coupling
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 109
year: '2021'
...
---
OA_place: publisher
OA_type: green
_id: '6995'
abstract:
- lang: eng
text: Human brain organoids represent a powerful tool for the study of human neurological
diseases particularly those that impact brain growth and structure. However, many
neurological diseases lack obvious anatomical abnormalities, yet significantly
impact neural network functions, raising the question of whether organoids possess
sufficient neural network architecture and complexity to model these conditions.
Here, we explore the network level functions of brain organoids using calcium
sensor imaging and extracellular recording approaches that together reveal the
existence of complex oscillatory network behaviors reminiscent of intact brain
preparations. We further demonstrate strikingly abnormal epileptiform network
activity in organoids derived from a Rett Syndrome patient despite only modest
anatomical differences from isogenically matched controls, and rescue with an
unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide
an essential foundation for the utilization of human brain organoids to study
intact and disordered human brain network formation and illustrate their utility
in therapeutic discovery.
acknowledgement: We thank S. Butler, T. Carmichael and members of the laboratory of
B.G.N. for helpful discussions and comments on the manuscript; N. Vishlaghi and
F. Turcios-Hernandez for technical assistance, and J. Lee, S.-K. Lee, H. Shinagawa
and K. Yoshikawa for valuable reagents. We also thank the UCLA Eli and Edythe Broad
Stem Cell Research Center (BSCRC) and Intellectual and Developmental Disabilities
Research Center microscopy cores for access to imaging facilities. This work was
supported by grants from the California Institute for Regenerative Medicine (CIRM)
(DISC1-08819 to B.G.N.), the National Institute of Health (R01NS089817, R01DA051897
and P50HD103557 to B.G.N.; K08NS119747 to R.A.S.; K99HD096105 to M.W.; R01MH123922,
R01MH121521 and P50HD103557 to M.J.G.; R01GM099134 to K.P.; R01NS103788 to W.E.L.;
R01NS088571 to J.M.P.; R01NS030549 and R01AG050474 to I.M.), and research awards
from the UCLA Jonsson Comprehensive Cancer Center and BSCRC Ablon Scholars Program
(to B.G.N.), the BSCRC Innovation Program (to B.G.N., K.P. and W.E.L.), the UCLA
BSCRC Steffy Brain Aging Research Fund (to B.G.N. and W.E.L.) and the UCLA Clinical
and Translational Science Institute (to B.G.N.), Paul Allen Family Foundation Frontiers
Group (to K.P. and W.E.L.), the March of Dimes Foundation (to W.E.L.) and the Simons
Foundation Autism Research Initiative Bridge to Independence Program (to R.A.S.
and M.J.G.). R.A.S. was also supported by the UCLA/NINDS Translational Neuroscience
Training Grant (R25NS065723), a Research and Training Fellowship from the American
Epilepsy Society, a Taking Flight Award from CURE Epilepsy and a Clinician Scientist
training award from the UCLA BSCRC. J.E.B. was supported by the UCLA BSCRC Rose
Hills Foundation Graduate Scholarship Training Program. M.W. was supported by postdoctoral
training awards provided by the UCLA BSCRC and the Uehara Memorial Foundation. O.A.M.
and A.K. were supported in part by the UCLA-California State University Northridge
CIRM-Bridges training program (EDUC2-08411). We also acknowledge the support of
the IDDRC Cells, Circuits and Systems Analysis, Microscopy and Genetics and Genomics
Cores of the Semel Institute of Neuroscience at UCLA, which are supported by the
NICHD (U54HD087101 and P50HD10355701). We lastly acknowledge support from a Quantitative
and Computational Biosciences Collaboratory Postdoctoral Fellowship to S.M. and
the Quantitative and Computational Biosciences Collaboratory community, directed
by M. Pellegrini.
article_processing_charge: No
article_type: review
author:
- first_name: Ranmal A.
full_name: Samarasinghe, Ranmal A.
last_name: Samarasinghe
- first_name: Osvaldo
full_name: Miranda, Osvaldo
id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
last_name: Miranda
orcid: 0000-0001-6618-6889
- first_name: Jessie E.
full_name: Buth, Jessie E.
last_name: Buth
- first_name: Simon
full_name: Mitchell, Simon
last_name: Mitchell
- first_name: Isabella
full_name: Ferando, Isabella
last_name: Ferando
- first_name: Momoko
full_name: Watanabe, Momoko
last_name: Watanabe
- first_name: Arinnae
full_name: Kurdian, Arinnae
last_name: Kurdian
- first_name: Peyman
full_name: Golshani, Peyman
last_name: Golshani
- first_name: Kathrin
full_name: Plath, Kathrin
last_name: Plath
- first_name: William E.
full_name: Lowry, William E.
last_name: Lowry
- first_name: Jack M.
full_name: Parent, Jack M.
last_name: Parent
- first_name: Istvan
full_name: Mody, Istvan
last_name: Mody
- first_name: Bennett G.
full_name: Novitch, Bennett G.
last_name: Novitch
citation:
ama: Samarasinghe RA, Miranda O, Buth JE, et al. Identification of neural oscillations
and epileptiform changes in human brain organoids. Nature Neuroscience.
2021;24:32. doi:10.1038/s41593-021-00906-5
apa: Samarasinghe, R. A., Miranda, O., Buth, J. E., Mitchell, S., Ferando, I., Watanabe,
M., … Novitch, B. G. (2021). Identification of neural oscillations and epileptiform
changes in human brain organoids. Nature Neuroscience. Springer Nature.
https://doi.org/10.1038/s41593-021-00906-5
chicago: Samarasinghe, Ranmal A., Osvaldo Miranda, Jessie E. Buth, Simon Mitchell,
Isabella Ferando, Momoko Watanabe, Arinnae Kurdian, et al. “Identification of
Neural Oscillations and Epileptiform Changes in Human Brain Organoids.” Nature
Neuroscience. Springer Nature, 2021. https://doi.org/10.1038/s41593-021-00906-5.
ieee: R. A. Samarasinghe et al., “Identification of neural oscillations and
epileptiform changes in human brain organoids,” Nature Neuroscience, vol.
24. Springer Nature, p. 32, 2021.
ista: Samarasinghe RA, Miranda O, Buth JE, Mitchell S, Ferando I, Watanabe M, Kurdian
A, Golshani P, Plath K, Lowry WE, Parent JM, Mody I, Novitch BG. 2021. Identification
of neural oscillations and epileptiform changes in human brain organoids. Nature
Neuroscience. 24, 32.
mla: Samarasinghe, Ranmal A., et al. “Identification of Neural Oscillations and
Epileptiform Changes in Human Brain Organoids.” Nature Neuroscience, vol.
24, Springer Nature, 2021, p. 32, doi:10.1038/s41593-021-00906-5.
short: R.A. Samarasinghe, O. Miranda, J.E. Buth, S. Mitchell, I. Ferando, M. Watanabe,
A. Kurdian, P. Golshani, K. Plath, W.E. Lowry, J.M. Parent, I. Mody, B.G. Novitch,
Nature Neuroscience 24 (2021) 32.
date_created: 2019-11-10T11:23:58Z
date_published: 2021-08-23T00:00:00Z
date_updated: 2025-07-09T09:00:12Z
day: '23'
department:
- _id: GradSch
- _id: SiHi
doi: 10.1038/s41593-021-00906-5
external_id:
isi:
- '000687516300001'
pmid:
- '34426698 '
intvolume: ' 24'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/820183
month: '08'
oa: 1
oa_version: Preprint
page: '32'
pmid: 1
publication: Nature Neuroscience
publication_identifier:
eissn:
- 1546-1726
issn:
- 1097-6256
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Identification of neural oscillations and epileptiform changes in human brain
organoids
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 24
year: '2021'
...
---
_id: '9906'
abstract:
- lang: eng
text: Endometriosis is a common gynecological disorder characterized by ectopic
growth of endometrium outside the uterus and is associated with chronic pain and
infertility. We investigated the role of the long intergenic noncoding RNA 01133
(LINC01133) in endometriosis, an lncRNA that has been implicated in several types
of cancer. We found that LINC01133 is upregulated in ectopic endometriotic lesions.
As expression appeared higher in the epithelial endometrial layer, we performed
a siRNA knockdown of LINC01133 in an endometriosis epithelial cell line. Phenotypic
assays indicated that LINC01133 may promote proliferation and suppress cellular
migration, and affect the cytoskeleton and morphology of the cells. Gene ontology
analysis of differentially expressed genes indicated that cell proliferation and
migration pathways were affected in line with the observed phenotype. We validated
upregulation of p21 and downregulation of Cyclin A at the protein level, which
together with the quantification of the DNA content using fluorescence-activated
cell sorting (FACS) analysis indicated that the observed effects on cellular proliferation
may be due to changes in cell cycle. Further, we found testis-specific protein
kinase 1 (TESK1) kinase upregulation corresponding with phosphorylation and inactivation
of actin severing protein Cofilin, which could explain changes in the cytoskeleton
and cellular migration. These results indicate that endometriosis is associated
with LINC01133 upregulation, which may affect pathogenesis via the cellular proliferation
and migration pathways.
acknowledgement: "Open access funding provided by Medical University of Vienna. The
authors would like to thank all the participants and health professionals involved
in the present study. We want to thank our technical assistants Barbara Widmar and
Matthias Witzmann-Stern for their diligent work and constant assistance. We would
like to thank Simon Hippenmeyer for access to\r\nbioinformatic infrastructure and
resources."
article_number: '8385'
article_processing_charge: Yes
article_type: original
author:
- first_name: Iveta
full_name: Yotova, Iveta
last_name: Yotova
- first_name: Quanah J.
full_name: Hudson, Quanah J.
last_name: Hudson
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Katharina
full_name: Proestling, Katharina
last_name: Proestling
- first_name: Isabella
full_name: Haslinger, Isabella
last_name: Haslinger
- first_name: Lorenz
full_name: Kuessel, Lorenz
last_name: Kuessel
- first_name: Alexandra
full_name: Perricos, Alexandra
last_name: Perricos
- first_name: Heinrich
full_name: Husslein, Heinrich
last_name: Husslein
- first_name: René
full_name: Wenzl, René
last_name: Wenzl
citation:
ama: Yotova I, Hudson QJ, Pauler F, et al. LINC01133 inhibits invasion and promotes
proliferation in an endometriosis epithelial cell line. International Journal
of Molecular Sciences. 2021;22(16). doi:10.3390/ijms22168385
apa: Yotova, I., Hudson, Q. J., Pauler, F., Proestling, K., Haslinger, I., Kuessel,
L., … Wenzl, R. (2021). LINC01133 inhibits invasion and promotes proliferation
in an endometriosis epithelial cell line. International Journal of Molecular
Sciences. MDPI. https://doi.org/10.3390/ijms22168385
chicago: Yotova, Iveta, Quanah J. Hudson, Florian Pauler, Katharina Proestling,
Isabella Haslinger, Lorenz Kuessel, Alexandra Perricos, Heinrich Husslein, and
René Wenzl. “LINC01133 Inhibits Invasion and Promotes Proliferation in an Endometriosis
Epithelial Cell Line.” International Journal of Molecular Sciences. MDPI,
2021. https://doi.org/10.3390/ijms22168385.
ieee: I. Yotova et al., “LINC01133 inhibits invasion and promotes proliferation
in an endometriosis epithelial cell line,” International Journal of Molecular
Sciences, vol. 22, no. 16. MDPI, 2021.
ista: Yotova I, Hudson QJ, Pauler F, Proestling K, Haslinger I, Kuessel L, Perricos
A, Husslein H, Wenzl R. 2021. LINC01133 inhibits invasion and promotes proliferation
in an endometriosis epithelial cell line. International Journal of Molecular Sciences.
22(16), 8385.
mla: Yotova, Iveta, et al. “LINC01133 Inhibits Invasion and Promotes Proliferation
in an Endometriosis Epithelial Cell Line.” International Journal of Molecular
Sciences, vol. 22, no. 16, 8385, MDPI, 2021, doi:10.3390/ijms22168385.
short: I. Yotova, Q.J. Hudson, F. Pauler, K. Proestling, I. Haslinger, L. Kuessel,
A. Perricos, H. Husslein, R. Wenzl, International Journal of Molecular Sciences
22 (2021).
date_created: 2021-08-15T22:01:27Z
date_published: 2021-08-04T00:00:00Z
date_updated: 2025-06-12T06:29:07Z
day: '04'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.3390/ijms22168385
external_id:
isi:
- '000689147400001'
pmid:
- '34445100'
file:
- access_level: open_access
checksum: be7f0042607ca60549cb27513c19c6af
content_type: application/pdf
creator: asandaue
date_created: 2021-08-16T09:29:17Z
date_updated: 2021-08-16T09:29:17Z
file_id: '9922'
file_name: 2021_InternationalJournalOfMolecularSciences_Yotova.pdf
file_size: 2646018
relation: main_file
success: 1
file_date_updated: 2021-08-16T09:29:17Z
has_accepted_license: '1'
intvolume: ' 22'
isi: 1
issue: '16'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
publication: International Journal of Molecular Sciences
publication_identifier:
eissn:
- 1422-0067
issn:
- 1661-6596
publication_status: published
publisher: MDPI
quality_controlled: '1'
scopus_import: '1'
status: public
title: LINC01133 inhibits invasion and promotes proliferation in an endometriosis
epithelial cell line
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 22
year: '2021'
...
---
_id: '8546'
abstract:
- lang: eng
text: Brain neurons arise from relatively few progenitors generating an enormous
diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain
neurogenesis is thought to be that excitatory and inhibitory neurons derive from
separate, spatially segregated progenitors. Whether bi-potential progenitors with
an intrinsic capacity to generate both lineages exist and how such a fate decision
may be regulated are unknown. Using cerebellar development as a model, we discover
that individual progenitors can give rise to both inhibitory and excitatory lineages.
Gradations of Notch activity determine the fates of the progenitors and their
daughters. Daughters with the highest levels of Notch activity retain the progenitor
fate, while intermediate levels of Notch activity generate inhibitory neurons,
and daughters with very low levels of Notch signaling adopt the excitatory fate.
Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating
the ratio of excitatory to inhibitory neurons from common progenitors.
acknowledgement: This work was supported by the program “Investissements d’avenir”
ANR-10-IAIHU-06 , ICM , a Sorbonne Université Emergence grant, an Allen Distinguished
Investigator Award , and the Roger De Spoelberch Foundation Prize (to B.A.H.); Armenise-Harvard
Foundation , AIRC , and CARITRO (to L.T.); and the European Research Council under
the European Union’s Horizon 2020 research and innovation programme grant agreement
no. 725780 LinPro (to S.H.). T.Z. and T.L. were supported by doctoral fellowships
from the China Scholarship Council and A.H.H. by a doctoral DOC fellowship of the
Austrian Academy of Sciences ( 24812 ). All animal work was conducted at the PHENO-ICMice
facility. The Core is supported by 2 “Investissements d’avenir” (ANR-10- IAIHU-06
and ANR-11-INBS-0011-NeurATRIS) and the “Fondation pour la Recherche Médicale.”
Light microscopy work was carried out at ICM’s imaging core facility, ICM.Quant,
and analysis of scRNA-seq data was carried out at ICM’s bioinformatics core facility,
iCONICS. We thank Paulina Ejsmont, Natalia Danda, and Nathalie De Geest for technical
support. We are grateful to Dr. Shahragim TAJBAKHSH for providing R26Rstop-NICD-nGFP
transgenic mice, Dr. Bart De Strooper for Psn1-deficient mice, Dr. Jean-Christophe
Marine for Gt(ROSA)26SortdTom reporter mice, and Dr. Martinez Barbera for Sox2CreERT2
mice. We also give thanks to Dr. Mikio Hoshino for providing Atoh1 and Ptf1a antibodies.
B.A.H. is an Einstein Visiting Fellow of the Berlin Institute of Health .
article_number: '109208'
article_processing_charge: No
article_type: original
author:
- first_name: Tingting
full_name: Zhang, Tingting
last_name: Zhang
- first_name: Tengyuan
full_name: Liu, Tengyuan
last_name: Liu
- first_name: Natalia
full_name: Mora, Natalia
last_name: Mora
- first_name: Justine
full_name: Guegan, Justine
last_name: Guegan
- first_name: Mathilde
full_name: Bertrand, Mathilde
last_name: Bertrand
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Andi H
full_name: Hansen, Andi H
id: 38853E16-F248-11E8-B48F-1D18A9856A87
last_name: Hansen
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Marica
full_name: Anderle, Marica
last_name: Anderle
- first_name: Natasha
full_name: Danda, Natasha
last_name: Danda
- first_name: Luca
full_name: Tiberi, Luca
last_name: Tiberi
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Bassem A.
full_name: Hassan, Bassem A.
last_name: Hassan
citation:
ama: Zhang T, Liu T, Mora N, et al. Generation of excitatory and inhibitory neurons
from common progenitors via Notch signaling in the cerebellum. Cell Reports.
2021;35(10). doi:10.1016/j.celrep.2021.109208
apa: Zhang, T., Liu, T., Mora, N., Guegan, J., Bertrand, M., Contreras, X., … Hassan,
B. A. (2021). Generation of excitatory and inhibitory neurons from common progenitors
via Notch signaling in the cerebellum. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2021.109208
chicago: Zhang, Tingting, Tengyuan Liu, Natalia Mora, Justine Guegan, Mathilde Bertrand,
Ximena Contreras, Andi H Hansen, et al. “Generation of Excitatory and Inhibitory
Neurons from Common Progenitors via Notch Signaling in the Cerebellum.” Cell
Reports. Elsevier, 2021. https://doi.org/10.1016/j.celrep.2021.109208.
ieee: T. Zhang et al., “Generation of excitatory and inhibitory neurons from
common progenitors via Notch signaling in the cerebellum,” Cell Reports,
vol. 35, no. 10. Elsevier, 2021.
ista: Zhang T, Liu T, Mora N, Guegan J, Bertrand M, Contreras X, Hansen AH, Streicher
C, Anderle M, Danda N, Tiberi L, Hippenmeyer S, Hassan BA. 2021. Generation of
excitatory and inhibitory neurons from common progenitors via Notch signaling
in the cerebellum. Cell Reports. 35(10), 109208.
mla: Zhang, Tingting, et al. “Generation of Excitatory and Inhibitory Neurons from
Common Progenitors via Notch Signaling in the Cerebellum.” Cell Reports,
vol. 35, no. 10, 109208, Elsevier, 2021, doi:10.1016/j.celrep.2021.109208.
short: T. Zhang, T. Liu, N. Mora, J. Guegan, M. Bertrand, X. Contreras, A.H. Hansen,
C. Streicher, M. Anderle, N. Danda, L. Tiberi, S. Hippenmeyer, B.A. Hassan, Cell
Reports 35 (2021).
date_created: 2020-09-21T12:00:48Z
date_published: 2021-06-08T00:00:00Z
date_updated: 2026-04-02T11:52:30Z
day: '08'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.celrep.2021.109208
ec_funded: 1
external_id:
isi:
- '000659894300001'
pmid:
- '34107249 '
file:
- access_level: open_access
checksum: 7def3d42ebc8f5675efb6f38819e3e2e
content_type: application/pdf
creator: cziletti
date_created: 2021-06-15T14:01:35Z
date_updated: 2021-06-15T14:01:35Z
file_id: '9554'
file_name: 2021_CellReports_Zhang.pdf
file_size: 8900385
relation: main_file
success: 1
file_date_updated: 2021-06-15T14:01:35Z
has_accepted_license: '1'
intvolume: ' 35'
isi: 1
issue: '10'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260018B0-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '725780'
name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development
- _id: 2625A13E-B435-11E9-9278-68D0E5697425
grant_number: '24812'
name: Molecular mechanisms of radial neuronal migration
publication: Cell Reports
publication_identifier:
eissn:
- ' 2211-1247'
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- relation: earlier_version
url: https://doi.org/10.1101/2020.03.18.997205
scopus_import: '1'
status: public
title: Generation of excitatory and inhibitory neurons from common progenitors via
Notch signaling in the cerebellum
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 35
year: '2021'
...
---
_id: '9601'
abstract:
- lang: eng
text: 'In mammalian genomes, differentially methylated regions (DMRs) and histone
marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted
genes are asymmetrically inherited to control parentally-biased gene expression.
However, neither parent-of-origin-specific transcription nor imprints have been
comprehensively mapped at the blastocyst stage of preimplantation development.
Here, we address this by integrating transcriptomic and epigenomic approaches
in mouse preimplantation embryos. We find that seventy-one genes exhibit previously
unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted
expressed). Uniparental expression of nBiX genes disappears soon after implantation.
Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts
detects 859 DMRs. We further find that 16% of nBiX genes are associated with a
DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a
role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered:
five clusters contained at least one published imprinted gene, and five clusters
exclusively contained nBiX genes. These data suggest that early development undergoes
a complex program of stage-specific imprinting involving different tiers of regulation.'
acknowledgement: The authors thank Robert Feil and Anton Wutz for helpful discussions
and comments, Samuel Collombet and Peter Fraser for sharing embryo TAD coordinates,
and Andy Riddel at the Cambridge Stem Cell Institute and Thomas Sauer at the Max
Perutz Laboratories FACS facility for flow-sorting. We thank the team of the Biomedical
Sequencing Facility at the CeMM and the Vienna Biocenter Core Facilities (VBCF)
for support with next-generation sequencing. We are grateful to animal care teams
at the University of Bath and MRC Harwell. A.C.F.P. acknowledges support from the
UK Medical Research Council (MR/N000080/1 and MR/N020294/1) and Biotechnology and
Biological Sciences Research Council (BB/P009506/1). L.S. is part of the FWF doctoral
programme SMICH and supported by an Austrian Academy of Sciences DOC Fellowship.
M.L. is funded by a Vienna Research Group for Young Investigators grant (VRG14-006)
by the Vienna Science and Technology Fund (WWTF) and by the Austrian Science Fund
FWF (I3786 and P31334).
article_number: '3804'
article_processing_charge: No
article_type: original
author:
- first_name: Laura
full_name: Santini, Laura
last_name: Santini
- first_name: Florian
full_name: Halbritter, Florian
last_name: Halbritter
- first_name: Fabian
full_name: Titz-Teixeira, Fabian
last_name: Titz-Teixeira
- first_name: Toru
full_name: Suzuki, Toru
last_name: Suzuki
- first_name: Maki
full_name: Asami, Maki
last_name: Asami
- first_name: Xiaoyan
full_name: Ma, Xiaoyan
last_name: Ma
- first_name: Julia
full_name: Ramesmayer, Julia
last_name: Ramesmayer
- first_name: Andreas
full_name: Lackner, Andreas
last_name: Lackner
- first_name: Nick
full_name: Warr, Nick
last_name: Warr
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Ernest
full_name: Laue, Ernest
last_name: Laue
- first_name: Matthias
full_name: Farlik, Matthias
last_name: Farlik
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
- first_name: Andreas
full_name: Beyer, Andreas
last_name: Beyer
- first_name: Anthony C.F.
full_name: Perry, Anthony C.F.
last_name: Perry
- first_name: Martin
full_name: Leeb, Martin
last_name: Leeb
citation:
ama: Santini L, Halbritter F, Titz-Teixeira F, et al. Genomic imprinting in mouse
blastocysts is predominantly associated with H3K27me3. Nature Communications.
2021;12(1). doi:10.1038/s41467-021-23510-4
apa: Santini, L., Halbritter, F., Titz-Teixeira, F., Suzuki, T., Asami, M., Ma,
X., … Leeb, M. (2021). Genomic imprinting in mouse blastocysts is predominantly
associated with H3K27me3. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23510-4
chicago: Santini, Laura, Florian Halbritter, Fabian Titz-Teixeira, Toru Suzuki,
Maki Asami, Xiaoyan Ma, Julia Ramesmayer, et al. “Genomic Imprinting in Mouse
Blastocysts Is Predominantly Associated with H3K27me3.” Nature Communications.
Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23510-4.
ieee: L. Santini et al., “Genomic imprinting in mouse blastocysts is predominantly
associated with H3K27me3,” Nature Communications, vol. 12, no. 1. Springer
Nature, 2021.
ista: Santini L, Halbritter F, Titz-Teixeira F, Suzuki T, Asami M, Ma X, Ramesmayer
J, Lackner A, Warr N, Pauler F, Hippenmeyer S, Laue E, Farlik M, Bock C, Beyer
A, Perry ACF, Leeb M. 2021. Genomic imprinting in mouse blastocysts is predominantly
associated with H3K27me3. Nature Communications. 12(1), 3804.
mla: Santini, Laura, et al. “Genomic Imprinting in Mouse Blastocysts Is Predominantly
Associated with H3K27me3.” Nature Communications, vol. 12, no. 1, 3804,
Springer Nature, 2021, doi:10.1038/s41467-021-23510-4.
short: L. Santini, F. Halbritter, F. Titz-Teixeira, T. Suzuki, M. Asami, X. Ma,
J. Ramesmayer, A. Lackner, N. Warr, F. Pauler, S. Hippenmeyer, E. Laue, M. Farlik,
C. Bock, A. Beyer, A.C.F. Perry, M. Leeb, Nature Communications 12 (2021).
date_created: 2021-06-27T22:01:46Z
date_published: 2021-07-12T00:00:00Z
date_updated: 2026-04-02T13:55:23Z
day: '12'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41467-021-23510-4
external_id:
isi:
- '000667248600005'
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creator: asandaue
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date_updated: 2021-06-28T08:04:22Z
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file_name: 2021_NatureCommunications_Santini.pdf
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success: 1
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language:
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month: '07'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 12
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...