---
OA_type: closed access
_id: '20972'
abstract:
- lang: eng
text: Small amounts of stress are thought to have beneficial effects. A new study
reports a mechanism by which the psychedelic drug, psilocybin, causes acute release
of stress hormones, despite its known long-term anti-anxiety effects.
article_processing_charge: No
article_type: letter_note
author:
- first_name: Hakan
full_name: Kücükdereli, Hakan
id: 5d5f6ea4-ef9e-11f0-a10a-85e12a3552af
last_name: Kücükdereli
- first_name: Amelia May Barnett
full_name: Douglass, Amelia May Barnett
id: de5f6fda-80fb-11ef-996f-a8c4ecd8e289
last_name: Douglass
orcid: 0000-0001-5398-6473
citation:
ama: 'Kücükdereli H, Douglass AM. Neuroscience: What doesn’t kill you makes you
stronger. Current Biology. 2026;36(1):R27-R29. doi:10.1016/j.cub.2025.11.056'
apa: 'Kücükdereli, H., & Douglass, A. M. (2026). Neuroscience: What doesn’t
kill you makes you stronger. Current Biology. Elsevier. https://doi.org/10.1016/j.cub.2025.11.056'
chicago: 'Kücükdereli, Hakan, and Amelia M. Douglass. “Neuroscience: What Doesn’t
Kill You Makes You Stronger.” Current Biology. Elsevier, 2026. https://doi.org/10.1016/j.cub.2025.11.056.'
ieee: 'H. Kücükdereli and A. M. Douglass, “Neuroscience: What doesn’t kill you makes
you stronger,” Current Biology, vol. 36, no. 1. Elsevier, pp. R27–R29,
2026.'
ista: 'Kücükdereli H, Douglass AM. 2026. Neuroscience: What doesn’t kill you makes
you stronger. Current Biology. 36(1), R27–R29.'
mla: 'Kücükdereli, Hakan, and Amelia M. Douglass. “Neuroscience: What Doesn’t Kill
You Makes You Stronger.” Current Biology, vol. 36, no. 1, Elsevier, 2026,
pp. R27–29, doi:10.1016/j.cub.2025.11.056.'
short: H. Kücükdereli, A.M. Douglass, Current Biology 36 (2026) R27–R29.
corr_author: '1'
date_created: 2026-01-11T23:01:33Z
date_published: 2026-01-05T00:00:00Z
date_updated: 2026-01-12T10:09:13Z
day: '05'
department:
- _id: AmDo
- _id: SiHi
doi: 10.1016/j.cub.2025.11.056
external_id:
pmid:
- '41494523'
fulldoi: https://doi.org/10.1016/j.cub.2025.11.056
intvolume: ' 36'
issue: '1'
language:
- iso: eng
month: '01'
oa_version: None
page: R27-R29
pmid: 1
publication: Current Biology
publication_identifier:
eissn:
- 1879-0445
issn:
- 0960-9822
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Neuroscience: What doesn’t kill you makes you stronger'
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 36
year: '2026'
...
---
OA_place: repository
OA_type: green
_id: '21212'
abstract:
- lang: eng
text: "Malignant glioma is incurable. Using a mouse genetic mosaic system to generate
sporadic Trp53,Nf1-null OPCs, we previously identified oligodendrocyte precursor
cell (OPC) as a cell-of-origin of glioma. Here, we report that pre-malignant Trp53,Nf1-null
OPCs outcompete wildtype counterparts during their expansion. Blocking competition
by mutating/strengthening wildtype OPCs impeded both pre-malignant progression
and malignant expansion of glioma.\r\n\r\n“In-tissue” phosphoproteomic profiling
revealed an enrichment of phosphopeptides related to RNA splicing and protein
translation at the peak of cell competition, suggesting that competitiveness may
stem from unique protein species. Among candidates was mTORC1, whose pharmacological
inhibition or genetic disruption resulted in a loss of competitiveness in our
mouse model. Finally, analysis of patient biopsies and interrogating the role
of individual gliomagenic mutations in OPC competition supported its relevance
in human gliomas. Together, these findings identified the driving role of competitive
interactions among OPCs in gliomagenesis, and suggest unconventional therapeutic
strategies to target this process."
acknowledgement: "We thank Dr. Wenjie Liu for providing critical feedback on the manuscript.
We also thank Dr.\r\nPat Pramoonjago at the Biorepository and Tissue Research Facility,
and Hope Davis at the\r\nvivarium for their assistance on the project. These Core
Facilities are supported by UVA Cancer\r\nCenter grant #P30-CA044579. We are grateful
to Dr. Jonathan A. Epstein for providing the\r\nNf1GRD/+ mouse strain (https://pubmed.ncbi.nlm.nih.gov/26460546/).
This work was partly\r\nsupported by the National Institute of Neurological Diseases
and Stroke R21 NS125479-01A1\r\n(H.Z.), American Cancer Society Institutional Research
Grant to the University of Virginia\r\n(Y.J.), the National Natural Science Foundation
of China #82072787 (M.Y.), the National\r\nCancer Institute U54 CA238114 (F.W.),
U01 CA284193 (K.M.N.), and U54 CA274499 (K.A.J.,\r\nM.F-S.), the National institute
of General Medical Sciences R35 GM133404 (M.F-S.), the Dr.\r\nMiriam and Sheldon
G. Adelson Medical Research Foundation (H.I.K., S.A.G.), the National\r\nCenter
for Advancing Translational Sciences KL2TR001882 (K.S.P.), Tower Cancer Career Development
Grant (K.S.P.), McKnight Neurobiology of Brain Disorders Grant (K.S.P.). The\r\ncontent
is solely the responsibility of the authors and does not necessarily represent the
official\r\nviews of the National Institutes of Health. Illustrations in this manuscript
were created with\r\nBioRender (BioRender.com)."
article_processing_charge: No
author:
- first_name: Ying
full_name: Jiang, Ying
last_name: Jiang
- first_name: Ryuhjin
full_name: Ahn, Ryuhjin
last_name: Ahn
- first_name: Arthur
full_name: Huang, Arthur
last_name: Huang
- first_name: Phillippe P.
full_name: Gonzalez, Phillippe P.
last_name: Gonzalez
- first_name: Jungeun
full_name: Kim, Jungeun
last_name: Kim
- first_name: Guoxin
full_name: Zhang, Guoxin
last_name: Zhang
- first_name: Zihao
full_name: Liu, Zihao
last_name: Liu
- first_name: Zhenqiang
full_name: He, Zhenqiang
last_name: He
- first_name: Lindsey
full_name: Dudley, Lindsey
last_name: Dudley
- first_name: Kunal S.
full_name: Patel, Kunal S.
last_name: Patel
- first_name: Godfrey A.
full_name: Dzhivhuho, Godfrey A.
last_name: Dzhivhuho
- first_name: Sam
full_name: Crowl, Sam
last_name: Crowl
- first_name: Piotr
full_name: Przanowski, Piotr
last_name: Przanowski
- first_name: Luisa Quesada
full_name: Camacho, Luisa Quesada
last_name: Camacho
- first_name: Sijie
full_name: Hao, Sijie
last_name: Hao
- first_name: Jianhao
full_name: Zeng, Jianhao
last_name: Zeng
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Mohammad
full_name: Fallahi-Sichani, Mohammad
last_name: Fallahi-Sichani
- first_name: Kevin A.
full_name: Janes, Kevin A.
last_name: Janes
- first_name: Kristen M.
full_name: Naegle, Kristen M.
last_name: Naegle
- first_name: Marie-Louise
full_name: Hammarskjold, Marie-Louise
last_name: Hammarskjold
- first_name: Steven A.
full_name: Goldman, Steven A.
last_name: Goldman
- first_name: Harley I.
full_name: Kornblum, Harley I.
last_name: Kornblum
- first_name: Maojin
full_name: Yao, Maojin
last_name: Yao
- first_name: Forest
full_name: White, Forest
last_name: White
- first_name: Hui
full_name: Zong, Hui
last_name: Zong
citation:
ama: Jiang Y, Ahn R, Huang A, et al. Critical role of cell competition in gliomagenesis.
bioRxiv. 2026. doi:10.64898/2026.01.15.699808
apa: Jiang, Y., Ahn, R., Huang, A., Gonzalez, P. P., Kim, J., Zhang, G., … Zong,
H. (2026). Critical role of cell competition in gliomagenesis. bioRxiv.
https://doi.org/10.64898/2026.01.15.699808
chicago: Jiang, Ying, Ryuhjin Ahn, Arthur Huang, Phillippe P. Gonzalez, Jungeun
Kim, Guoxin Zhang, Zihao Liu, et al. “Critical Role of Cell Competition in Gliomagenesis.”
BioRxiv, 2026. https://doi.org/10.64898/2026.01.15.699808.
ieee: Y. Jiang et al., “Critical role of cell competition in gliomagenesis,”
bioRxiv. 2026.
ista: Jiang Y, Ahn R, Huang A, Gonzalez PP, Kim J, Zhang G, Liu Z, He Z, Dudley
L, Patel KS, Dzhivhuho GA, Crowl S, Przanowski P, Camacho LQ, Hao S, Zeng J, Hippenmeyer
S, Fallahi-Sichani M, Janes KA, Naegle KM, Hammarskjold M-L, Goldman SA, Kornblum
HI, Yao M, White F, Zong H. 2026. Critical role of cell competition in gliomagenesis.
bioRxiv, 10.64898/2026.01.15.699808.
mla: Jiang, Ying, et al. “Critical Role of Cell Competition in Gliomagenesis.” BioRxiv,
2026, doi:10.64898/2026.01.15.699808.
short: Y. Jiang, R. Ahn, A. Huang, P.P. Gonzalez, J. Kim, G. Zhang, Z. Liu, Z. He,
L. Dudley, K.S. Patel, G.A. Dzhivhuho, S. Crowl, P. Przanowski, L.Q. Camacho,
S. Hao, J. Zeng, S. Hippenmeyer, M. Fallahi-Sichani, K.A. Janes, K.M. Naegle,
M.-L. Hammarskjold, S.A. Goldman, H.I. Kornblum, M. Yao, F. White, H. Zong, BioRxiv
(2026).
date_created: 2026-02-10T12:55:55Z
date_published: 2026-01-16T00:00:00Z
date_updated: 2026-02-16T10:12:42Z
day: '16'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.64898/2026.01.15.699808
fulldoi: https://doi.org/10.64898/2026.01.15.699808
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.64898/2026.01.15.699808
month: '01'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: published
status: public
title: Critical role of cell competition in gliomagenesis
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: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
OA_place: repository
OA_type: green
_id: '21290'
abstract:
- lang: eng
text: Gene duplication underlies evolutionary innovation, yet many paralogues remain
highly similar, raising questions about their functional divergence and physiological
relevance. The spliceosomal Sm core protein SNRPB and its mammalian-specific paralogue
SNRPN share over 90% sequence identity, but their distinct expression patterns
- SNRPB being ubiquitous and SNRPN confined to the brain - suggest specialized
functions. Why mammals have two different spliceosomes has remained obscure. Here,
we generated isogenic human cell lines expressing ectopically either SNRPB or
SNRPN exclusively and found that SNRPN stabilizes transcripts involved in energy
metabolism and mitochondrial function, leading to increased mitochondrial abundance
and oxygen consumption. Despite similar spliceosomal interactomes, SNRPN more
strongly associates with the PRMT5 methylosome complex and exhibits dynamic arginine
methylation in its C-terminal region that is sensitive to translation inhibition
and amino acid availability. The SNRPN-dependent transcriptome responds to translation
inhibition by stabilizing long, intron-rich genes involved in amino acid and energy
metabolism. Our findings reveal a nutrient-sensitive, methylation-dependent mechanism
that differentiates the two paralogues. This suggests that SNRPN functions as
a metabolic-specialized spliceosomal subunit thereby providing tissue-specific
adaptation of RNA processing in mammals.
acknowledgement: "We thank Oliver Mühlemann and Alex Hofer (University of Bern) for
sharing SMG inhibitors\r\nand for their expertise in nonsense-mediated mRNA decay
and Maria Hondele for critical\r\nreading of the manuscript draft. We also thank
the IMB Genomics Core Facility for assistance\r\nwith library preparation and sequencing,
Martin Möckel and the IMB Protein Production Core\r\nFacility for providing enzymes
used in this work, Marton Gelleri together with the IMB\r\nMicroscopy Core Facility
for support with microscopy and FRAP experiments, Jasmin Cartano\r\nfor proteomics
sample processing and the IMB Flow Cytometry Core Facility for support. In\r\naddition,
we thank the Imaging Core Facility (IMCF) and the FACS Core Facility at the\r\nBiozentrum,
University of Basel, for technical assistance. CIKV acknowledges funding by the\r\nDeutsche
Forschungsgemeinschaft (DFG, German Research Foundation) - Individual Grant\r\nProject
no. 513744403, Scientific Network Grant Project no. 531902894, GRK2526 “Genevo”\r\n-
Project no. 407023052”, GRK2859 (“4R”) - Project no. 491145305, Forschungsinitiative\r\nRheinland-Pfalz
(ReALity), the EMBO Young Investigator Program (5795), institutional\r\nfunding
from the Institute of Molecular Biology and funds from the Kanton Basel-Stadt and\r\nBasel-Land
provided to the Biozentrum of the University Basel. J.H.G.F.G. was part of the\r\n‘Science
of Healthy Ageing Research Programme’ (SHARP) initiative funded by RhinelandPalatinate’s
Ministry of Science, Education and Culture. PR is funded by the Biozentrum PhD\r\nFellowships
Program. MFB received financial support from the intramural High Potentials\r\nGrant
program of the University Medical Center Mainz, Forschungsinitiative Rheinland-Pfalz\r\n(ReALity)
and Stiftungen zugunsten der Medizinischen Fakultät der LMU Klinikum (26069).\r\nInstruments
in the IMB core facilities were supported by funds from the DFG: Laser Scanning\r\nConfocal
(Leica Stellaris 8 Falcon, funded by the DFG - Project #497669232), Orbitrap Astral
system (funded by the DFG - Project #524805621) and BD LSRFortessa SOPR is funded
by\r\nthe DFG - Project #210253511.\r\n"
article_processing_charge: No
author:
- first_name: Feyza
full_name: Polat Haas, Feyza
last_name: Polat Haas
- first_name: Ana
full_name: Villalba Requena, Ana
id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
last_name: Villalba Requena
orcid: 0000-0002-5615-5277
- first_name: Polina
full_name: Rusina, Polina
last_name: Rusina
- first_name: Anusha
full_name: Gopalan, Anusha
last_name: Gopalan
- first_name: Hector
full_name: Fritz, Hector
last_name: Fritz
- first_name: Azamat
full_name: Akhmetkaliyev, Azamat
last_name: Akhmetkaliyev
- first_name: Frank
full_name: Ruehle, Frank
last_name: Ruehle
- first_name: Anna
full_name: Einsiedel, Anna
last_name: Einsiedel
- first_name: Anna
full_name: Szczepinska, Anna
last_name: Szczepinska
- first_name: Fridolin
full_name: Kielisch, Fridolin
last_name: Kielisch
- first_name: Jia-Xuan
full_name: Chen, Jia-Xuan
last_name: Chen
- first_name: Susanne
full_name: Nguyen, Susanne
last_name: Nguyen
- first_name: Thierry
full_name: Schmidlin, Thierry
last_name: Schmidlin
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: M. Felicia
full_name: Bailicata, M. Felicia
last_name: Bailicata
- first_name: Claudia Isabelle
full_name: Keller Valsecchi, Claudia Isabelle
last_name: Keller Valsecchi
citation:
ama: Polat Haas F, Villalba Requena A, Rusina P, et al. The splicing paralogues
SNRPB and SNRPN control differential metabolic states. bioRxiv. doi:10.64898/2026.02.11.705284
apa: Polat Haas, F., Villalba Requena, A., Rusina, P., Gopalan, A., Fritz, H., Akhmetkaliyev,
A., … Keller Valsecchi, C. I. (n.d.). The splicing paralogues SNRPB and SNRPN
control differential metabolic states. bioRxiv. https://doi.org/10.64898/2026.02.11.705284
chicago: Polat Haas, Feyza, Ana Villalba Requena, Polina Rusina, Anusha Gopalan,
Hector Fritz, Azamat Akhmetkaliyev, Frank Ruehle, et al. “The Splicing Paralogues
SNRPB and SNRPN Control Differential Metabolic States.” BioRxiv, n.d. https://doi.org/10.64898/2026.02.11.705284.
ieee: F. Polat Haas et al., “The splicing paralogues SNRPB and SNRPN control
differential metabolic states.,” bioRxiv. .
ista: Polat Haas F, Villalba Requena A, Rusina P, Gopalan A, Fritz H, Akhmetkaliyev
A, Ruehle F, Einsiedel A, Szczepinska A, Kielisch F, Chen J-X, Nguyen S, Schmidlin
T, Hippenmeyer S, Bailicata MF, Keller Valsecchi CI. The splicing paralogues SNRPB
and SNRPN control differential metabolic states. bioRxiv, 10.64898/2026.02.11.705284.
mla: Polat Haas, Feyza, et al. “The Splicing Paralogues SNRPB and SNRPN Control
Differential Metabolic States.” BioRxiv, doi:10.64898/2026.02.11.705284.
short: F. Polat Haas, A. Villalba Requena, P. Rusina, A. Gopalan, H. Fritz, A. Akhmetkaliyev,
F. Ruehle, A. Einsiedel, A. Szczepinska, F. Kielisch, J.-X. Chen, S. Nguyen, T.
Schmidlin, S. Hippenmeyer, M.F. Bailicata, C.I. Keller Valsecchi, BioRxiv (n.d.).
date_created: 2026-02-17T11:35:59Z
date_published: 2026-02-11T00:00:00Z
date_updated: 2026-02-23T11:03:33Z
day: '11'
department:
- _id: SiHi
doi: 10.64898/2026.02.11.705284
fulldoi: https://doi.org/10.64898/2026.02.11.705284
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.64898/2026.02.11.705284
month: '02'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
status: public
title: The splicing paralogues SNRPB and SNRPN control differential metabolic states.
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
OA_place: repository
OA_type: green
_id: '21291'
abstract:
- lang: eng
text: The complexity and specificity of movement in vertebrates is driven by a rich
diversity of spinal motor and interneuron cell types. During development, eleven
spinal cord progenitor domains generate an equivalent number of cardinal neuron
types. How progenitor domains, individual progenitors, and post-mitotic diversity
relate is still unknown. We performed high-resolution, single-progenitor cell
lineage tracing in the embryonic mouse spinal cord using mosaic analysis with
double markers (MADM). Our quantitative study of lineage progression revealed
that spinal cord progenitors undergo highly variable numbers of proliferative,
neurogenic, and gliogenic cell divisions. The nascent clonally-related neurons
migrate radially over large distances, span the dorsoventral axis, and even cross
the midline, demonstrating striking bilaterality. Molecular and morphometric analysis
indicate high levels of progenitor multipotency, with an individual progenitor
capable of producing several molecularly and morphologically distinct neuron types,
as well as astrocytes. These findings redefine spinal cord development as a process
in which lineage variability — rather than rigid progenitor identity — drives
the generation of cellular diversity.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
acknowledgement: "We would like to thank Elizabeth Marin, Anna Kicheva, Igor Adameyko,
and James Briscoe as\r\nwell as members of the Sweeney and Hippemeyer labs and SFB
consortium for comments on\r\nthe manuscript. We are also grateful for the technical
support of the Preclinical and Imaging and\r\nOptics Facilities support teams (ISTA).
In addition, we thank our funding sources for providing\r\nthe resources to do these
experiments: Horizon Europe ERC Starting Grant Number 101041551\r\n(M.S.; L.B.S.);
Special Research Program (SFB) of the Austrian Science Fund (FWF)\r\nNeuroStem Modulation
Project numbers F7814-B (S.A.G.; M.S.; G.S.; and L.B.S.) and F7805\r\n(G.C. and
S.H.). S.A.G is supported by a Boehringer Ingelheim Fonds PhD Fellowship, F.D.S.N.\r\nby
an Institute of Science and Technology Austria (ISTA) GROW fellowship, and G.C.
by an\r\nISTA Plus postdoctoral fellowship from the European Commission. S.H./L.B.S.
and G.C. were\r\nadditionally supported by institutional funds from the ISTA and
the University of Exeter,\r\nrespectively. "
article_processing_charge: No
author:
- first_name: Sophie A
full_name: Gobeil, Sophie A
id: 2f3e9efb-eb24-11ec-86b2-88efb11d59fa
last_name: Gobeil
- first_name: Francisco
full_name: Da Silveira Neto, Francisco
id: 8cfb7412-10a7-11f1-add1-82b44e6418f2
last_name: Da Silveira Neto
- first_name: Giulia
full_name: Silvestrelli, Giulia
id: 12632ae8-799e-11ef-94a2-e5a3b5ef49e9
last_name: Silvestrelli
- first_name: Matthijs Geert
full_name: Smits, Matthijs Geert
id: 7a231d52-e216-11ee-a0bb-8acd55f8f1f0
last_name: Smits
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- 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: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Lora Beatrice Jaeger
full_name: Sweeney, Lora Beatrice Jaeger
id: 56BE8254-C4F0-11E9-8E45-0B23E6697425
last_name: Sweeney
orcid: 0000-0001-9242-5601
citation:
ama: Gobeil SA, Da Silveira Neto F, Silvestrelli G, et al. Lineage origin of spinal
cord cell type diversity. bioRxiv. doi:10.64898/2026.02.12.705305
apa: Gobeil, S. A., Da Silveira Neto, F., Silvestrelli, G., Smits, M. G., Streicher,
C., Cheung, G. T., … Sweeney, L. B. (n.d.). Lineage origin of spinal cord cell
type diversity. bioRxiv. https://doi.org/10.64898/2026.02.12.705305
chicago: Gobeil, Sophie A, Francisco Da Silveira Neto, Giulia Silvestrelli, Matthijs
Geert Smits, Carmen Streicher, Giselle T Cheung, Simon Hippenmeyer, and Lora B.
Sweeney. “Lineage Origin of Spinal Cord Cell Type Diversity.” BioRxiv,
n.d. https://doi.org/10.64898/2026.02.12.705305.
ieee: S. A. Gobeil et al., “Lineage origin of spinal cord cell type diversity,”
bioRxiv. .
ista: Gobeil SA, Da Silveira Neto F, Silvestrelli G, Smits MG, Streicher C, Cheung
GT, Hippenmeyer S, Sweeney LB. Lineage origin of spinal cord cell type diversity.
bioRxiv, 10.64898/2026.02.12.705305.
mla: Gobeil, Sophie A., et al. “Lineage Origin of Spinal Cord Cell Type Diversity.”
BioRxiv, doi:10.64898/2026.02.12.705305.
short: S.A. Gobeil, F. Da Silveira Neto, G. Silvestrelli, M.G. Smits, C. Streicher,
G.T. Cheung, S. Hippenmeyer, L.B. Sweeney, BioRxiv (n.d.).
corr_author: '1'
date_created: 2026-02-17T11:36:20Z
date_published: 2026-02-16T00:00:00Z
date_updated: 2026-04-14T08:16:55Z
day: '16'
ddc:
- '570'
department:
- _id: SiHi
- _id: LoSw
doi: 10.64898/2026.02.12.705305
fulldoi: https://doi.org/10.64898/2026.02.12.705305
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.64898/2026.02.12.705305
month: '02'
oa: 1
oa_version: Preprint
project:
- _id: ebb66355-77a9-11ec-83b8-b8ac210a4dae
grant_number: '101041551'
name: Development and Evolution of Tetrapod Motor Circuits
- _id: 8da85f50-16d5-11f0-9cad-eab8b0ff6c9e
grant_number: F7814
name: 'Stem Cell Modulation in Neural Development and Regeneration/ P14-Swim-to-limb
transition: cell type to connection diversity'
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
publication: bioRxiv
publication_status: submitted
status: public
title: Lineage origin of spinal cord cell type diversity
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: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
OA_place: repository
OA_type: green
_id: '21962'
abstract:
- lang: eng
text: The generation of faithful cell-type diversity and correct projection neuron
numbers is essential for cerebral cortex development. Corticogenesis is however
susceptible to genetic interference of critical signaling pathways, including
mutations in Mtor/Rptor that lead to microcephaly. How the loss of Rptor/mTORC1
function affects cortical developmental programs, at single cell level, is still
unknown. Here, we utilized Mosaic Analysis with Double Markers (MADM) technology
to probe Rptor gene function upon sparse single cell- or global tissue-wide ablation.
We found that tissue-wide effects drive the etiology of cortical microcephaly
upon loss of Rptor, rather than deficits in projection neuron genesis. Conversely,
Rptor function is cell-autonomously required for postnatal projection neuron survival
in a highly cell-type-specific manner. Collectively, our results suggest that
the fine balance of precise cell-type-specific cell-autonomous Rptor/mTORC1 function
in concert with non-cell-autonomous tissue-wide effects is essential for the development
of a properly-sized cerebral cortex with accurate projection neuron diversity.
acknowledged_ssus:
- _id: PreCl
- _id: LifeSc
- _id: MassSpec
- _id: Bio
acknowledgement: "We thank A. Heger (IST Austria Preclinical Facility), A. Sommer
(VBCF GmbH, NGS Unit), and A.\r\nNicolas (IST Austria Lab Support Facility / Mass
Spectrometry Facility) for technical support; K. Ferencak,\r\nI. Aykara, P. Hirschfeld,
E. Fisher, S. Laukoter, L. Andersen for initial experiments and/or assistance; and\r\nall
members of the Hippenmeyer lab for discussion. This research was supported by the
Scientific Service\r\nUnits (SSU) of IST Austria through resources provided by the
Imaging and Optics- (IOF), Lab Support-\r\n(LSF) and Preclinical Facilities (PCF).
R.B. received support from FWF Meitner-Programm (M 2416). This\r\nwork was also
supported by IST Austria institutional funds; the People Programme (Marie Curie
Actions)\r\nof the European Union’s Seventh Framework Programme (FP7/2007-2013)
under REA grant agreement\r\nNo 618444 to S.H., and the European Research Council
(ERC) under the European Union’s Horizon 2020\r\nresearch and innovation programme
(grant agreement No 725780 LinPro) to S.H."
article_processing_charge: No
author:
- first_name: Ana
full_name: Villalba Requena, Ana
id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
last_name: Villalba Requena
orcid: 0000-0002-5615-5277
- first_name: Robert J
full_name: Beattie, Robert J
id: 2E26DF60-F248-11E8-B48F-1D18A9856A87
last_name: Beattie
orcid: 0000-0002-8483-8753
- 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: Osvaldo
full_name: Miranda, Osvaldo
id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
last_name: Miranda
orcid: 0000-0001-6618-6889
- first_name: Thomas
full_name: Krausgruber, Thomas
last_name: Krausgruber
- first_name: Martin
full_name: Senekowitsch, Martin
last_name: Senekowitsch
- first_name: Matthias
full_name: Farlik, Matthias
last_name: Farlik
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
- 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: Villalba Requena A, Beattie RJ, Pauler F, et al. Mtor/Rptor function globally
prevents cortical microcephaly and cell-autonomously promotes postnatal neuron
survival in cell type specific manner. bioRxiv. doi:10.64898/2026.05.01.722172
apa: Villalba Requena, A., Beattie, R. J., Pauler, F., Streicher, C., Miranda, O.,
Krausgruber, T., … Hippenmeyer, S. (n.d.). Mtor/Rptor function globally prevents
cortical microcephaly and cell-autonomously promotes postnatal neuron survival
in cell type specific manner. bioRxiv. https://doi.org/10.64898/2026.05.01.722172
chicago: Villalba Requena, Ana, Robert J Beattie, Florian Pauler, Carmen Streicher,
Osvaldo Miranda, Thomas Krausgruber, Martin Senekowitsch, et al. “Mtor/Rptor Function
Globally Prevents Cortical Microcephaly and Cell-Autonomously Promotes Postnatal
Neuron Survival in Cell Type Specific Manner.” BioRxiv, n.d. https://doi.org/10.64898/2026.05.01.722172.
ieee: A. Villalba Requena et al., “Mtor/Rptor function globally prevents
cortical microcephaly and cell-autonomously promotes postnatal neuron survival
in cell type specific manner,” bioRxiv. .
ista: Villalba Requena A, Beattie RJ, Pauler F, Streicher C, Miranda O, Krausgruber
T, Senekowitsch M, Farlik M, Bock C, Rülicke T, Hippenmeyer S. Mtor/Rptor function
globally prevents cortical microcephaly and cell-autonomously promotes postnatal
neuron survival in cell type specific manner. bioRxiv, 10.64898/2026.05.01.722172.
mla: Villalba Requena, Ana, et al. “Mtor/Rptor Function Globally Prevents Cortical
Microcephaly and Cell-Autonomously Promotes Postnatal Neuron Survival in Cell
Type Specific Manner.” BioRxiv, doi:10.64898/2026.05.01.722172.
short: A. Villalba Requena, R.J. Beattie, F. Pauler, C. Streicher, O. Miranda, T.
Krausgruber, M. Senekowitsch, M. Farlik, C. Bock, T. Rülicke, S. Hippenmeyer,
BioRxiv (n.d.).
date_created: 2026-06-09T08:08:18Z
date_published: 2026-05-05T00:00:00Z
date_updated: 2026-06-16T08:45:25Z
day: '05'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.64898/2026.05.01.722172
ec_funded: 1
fulldoi: https://doi.org/10.64898/2026.05.01.722172
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.64898/2026.05.01.722172
month: '05'
oa: 1
oa_version: Preprint
project:
- _id: 264E56E2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: M02416
name: Molecular Mechanisms Regulating Gliogenesis in the Neocortex
- _id: 25D61E48-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618444'
name: Molecular Mechanisms of Cerebral Cortex Development
- _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
status: public
title: Mtor/Rptor function globally prevents cortical microcephaly and cell-autonomously
promotes postnatal neuron survival in cell type specific manner
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
OA_place: repository
OA_type: green
_id: '21963'
abstract:
- lang: eng
text: The cerebral cortex consists of immense numbers of neuronal and glial cell-types
derived from radial glial progenitor (RGP) cells. How RGPs generate appropriate
quantities of distinct cortical cell-types to safeguard a brain of correct size,
is not well understood. However, genetic aberration in human, including mutations
in PTEN, lead to cortical malformation such as macrocephaly, albeit with unknown
etiology. Here we utilized Mosaic Analysis with Double Markers (MADM)-based clonal
analysis and single cell phenotyping to decipher the role of Pten in neurogenic
and gliogenic RGP lineage progression during cortical ontogeny. While neurogenic
RGP lineage progression and projection neuron production was moderately altered
in the absence of Pten, cortical astrocyte production was drastically increased.
Through genetic epistasis experiments we show that the loss of Pten uncouples
astrocyte generation from essential growth factor signaling hubs, funneling into
MAPK. Collectively, our results suggest that Pten regulates RGP lineage progression
with distinct sequential functions in cortical projection neurogenesis and astrocyte
production to ensure the emergence of a correctly-sized cerebral cortex.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: "We thank Kay-Uwe Wagner (Wayne State University) for generously
sharing Jak1/2–flox mouse lines; A.\r\nSommer (VBCF GmbH, NGS Unit) for technical
support; N. Kim, V. Mick, S. Schnabl, S. Gobeil, and L.\r\nAndersen for technical
assistance; all members of the Hippenmeyer lab for discussion and B. Novitch for\r\ncomments
on earlier versions of the manuscript. This research was supported by the Scientific
Service Units\r\n(SSU) of IST Austria through resources provided by the Imaging
and Optics Facility (IOF), Lab Support-\r\n(LSF) and Preclinical Facilities (PCF).
O.A.M received support from the Austrian Academy of Sciences\r\nÖAW (DOC 186584),
and N.A. from FWF Elise Richter Program (Grant V1041T). This work was also\r\nsupported
by IST Austria institutional funds; FWF SFB F78 (Neuro Stem Modulation) to S.H.,
and the\r\nEuropean Research Council (ERC) under the European Union’s Horizon 2020
research and innovation\r\nprogramme (grant agreement No 725780 LinPro) to S.H."
article_processing_charge: No
author:
- first_name: Osvaldo
full_name: Miranda, Osvaldo
id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
last_name: Miranda
orcid: 0000-0001-6618-6889
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Amarbayasgalan
full_name: Davaatseren, Amarbayasgalan
id: 70ADC922-B424-11E9-99E3-BA18E6697425
last_name: Davaatseren
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Ana
full_name: Villalba Requena, Ana
id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
last_name: Villalba Requena
orcid: 0000-0002-5615-5277
- first_name: Anna-Magdalena
full_name: Heger, Anna-Magdalena
id: 4B76FFD2-F248-11E8-B48F-1D18A9856A87
last_name: Heger
- first_name: Corentine
full_name: Marie, Corentine
last_name: Marie
- first_name: Bassem A.
full_name: Hassan, Bassem A.
last_name: Hassan
- 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: Miranda O, Contreras X, Pauler F, et al. Pten orchestrates neurogenic radial
glia lineage progression and tunes neocortical astrocyte production. bioRxiv.
doi:10.64898/2026.05.01.722191
apa: Miranda, O., Contreras, X., Pauler, F., Davaatseren, A., Amberg, N., Streicher,
C., … Hippenmeyer, S. (n.d.). Pten orchestrates neurogenic radial glia lineage
progression and tunes neocortical astrocyte production. bioRxiv. https://doi.org/10.64898/2026.05.01.722191
chicago: Miranda, Osvaldo, Ximena Contreras, Florian Pauler, Amarbayasgalan Davaatseren,
Nicole Amberg, Carmen Streicher, Ana Villalba Requena, et al. “Pten Orchestrates
Neurogenic Radial Glia Lineage Progression and Tunes Neocortical Astrocyte Production.”
BioRxiv, n.d. https://doi.org/10.64898/2026.05.01.722191.
ieee: O. Miranda et al., “Pten orchestrates neurogenic radial glia lineage
progression and tunes neocortical astrocyte production,” bioRxiv. .
ista: Miranda O, Contreras X, Pauler F, Davaatseren A, Amberg N, Streicher C, Villalba
Requena A, Heger A-M, Marie C, Hassan BA, Rülicke T, Hippenmeyer S. Pten orchestrates
neurogenic radial glia lineage progression and tunes neocortical astrocyte production.
bioRxiv, 10.64898/2026.05.01.722191.
mla: Miranda, Osvaldo, et al. “Pten Orchestrates Neurogenic Radial Glia Lineage
Progression and Tunes Neocortical Astrocyte Production.” BioRxiv, doi:10.64898/2026.05.01.722191.
short: O. Miranda, X. Contreras, F. Pauler, A. Davaatseren, N. Amberg, C. Streicher,
A. Villalba Requena, A.-M. Heger, C. Marie, B.A. Hassan, T. Rülicke, S. Hippenmeyer,
BioRxiv (n.d.).
corr_author: '1'
date_created: 2026-06-09T08:08:53Z
date_published: 2026-05-05T00:00:00Z
date_updated: 2026-06-16T08:57:20Z
day: '05'
ddc:
- '570'
department:
- _id: SiHi
- _id: PreCl
- _id: GradSch
doi: 10.64898/2026.05.01.722191
ec_funded: 1
fulldoi: https://doi.org/10.64898/2026.05.01.722191
has_accepted_license: '1'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.64898/2026.05.01.722191
month: '05'
oa: 1
oa_version: Preprint
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
- _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
status: public
title: Pten orchestrates neurogenic radial glia lineage progression and tunes neocortical
astrocyte production
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '22714'
abstract:
- lang: eng
text: Radial glial progenitors (RGPs) generate all projection neurons (PNs) in the
cerebral cortex through incompletely understood processes. We combined Mosaic
Analysis with Double Markers at embryonic stages (E)12.5 and E13.5 with early
postnatal callosal tracing to dissect RGP lineage progression. We find that multipotent
RGPs generate all extra-telencephalic (ET) and intra-telencephalic (IT) PNs via
parallel sublineages that emerge simultaneously at neurogenesis onset. ET-PN production
progresses exclusively via small, self-consuming lineages; IT-PN lineages feature
RGPs generating large translaminar outputs. The early emergence of IT-PN–fated
RGPs, coinciding with a switch to direct neurogenesis, contributes to the stereotyped
population-level progression of the multipotent lineage. We also identify POU3F
transcription factors as candidate regulators of IT-PN fate via noncanonical mitotic
chromatin binding. The results support a model whereby IT- and ET-PNs arise from
an early bifurcation and parallel specification within the multipotent RGP lineage.
acknowledgement: 'We thank M. caouyette for the plasmid construction for Pou3f1overexpression;
d. Pinto-Benito for valuable assistance with shRnA validation in n2A cells andqPcR
experiments; c. Varela-Martínez for help with the code for graphical analysis; allmembers
from the nieto’s lab for comment on the manuscript, specially to F. Martín for theinsightful
discussions; J. c. Oliveros and J. A. García from the computational service of the
cnBfor help with the analysis of RnAseq dataset; c. O. Sorzano for help with statistical
analysis; andA. Oña and the service of Advance Optical Microscopy of the cnB for
technical advice.Funding: i.V.-M. holds a fellowship funded by MciciU (PRe-2018-083376)
and 2023 eMBOscientific exchange grant 10214. the work was funded by grants to M.n.
(Pid2020-112831GB- i00 and Pid2023-146322nB- i00 by Mcin/Aei/10.13039/501100011033
and by“eRdF A way of making europe”).'
article_processing_charge: Yes
article_type: original
author:
- first_name: Irene
full_name: Varela Martínez, Irene
id: a69b5985-8829-11f0-8fc2-d0af58f64471
last_name: Varela Martínez
- first_name: Ana
full_name: Villalba Requena, Ana
id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
last_name: Villalba Requena
orcid: 0000-0002-5615-5277
- first_name: Jorge
full_name: García-Marqués, Jorge
last_name: García-Marqués
- first_name: Alfonso
full_name: Aguilera, Alfonso
last_name: Aguilera
- first_name: Diogo S.
full_name: Castro, Diogo S.
last_name: Castro
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Marta
full_name: Nieto, Marta
last_name: Nieto
citation:
ama: Varela Martínez I, Villalba Requena A, García-Marqués J, et al. Early fate
diversification of radial glial progenitors during corticogenesis. Science
Advances. 2026;12(32):eadw5487. doi:10.1126/sciadv.adw5487
apa: Varela Martínez, I., Villalba Requena, A., García-Marqués, J., Aguilera, A.,
Castro, D. S., Hippenmeyer, S., & Nieto, M. (2026). Early fate diversification
of radial glial progenitors during corticogenesis. Science Advances. AAAS.
https://doi.org/10.1126/sciadv.adw5487
chicago: Varela Martínez, Irene, Ana Villalba Requena, Jorge García-Marqués, Alfonso
Aguilera, Diogo S. Castro, Simon Hippenmeyer, and Marta Nieto. “Early Fate Diversification
of Radial Glial Progenitors during Corticogenesis.” Science Advances. AAAS,
2026. https://doi.org/10.1126/sciadv.adw5487.
ieee: I. Varela Martínez et al., “Early fate diversification of radial glial
progenitors during corticogenesis,” Science Advances, vol. 12, no. 32.
AAAS, p. eadw5487, 2026.
ista: Varela Martínez I, Villalba Requena A, García-Marqués J, Aguilera A, Castro
DS, Hippenmeyer S, Nieto M. 2026. Early fate diversification of radial glial progenitors
during corticogenesis. Science Advances. 12(32), eadw5487.
mla: Varela Martínez, Irene, et al. “Early Fate Diversification of Radial Glial
Progenitors during Corticogenesis.” Science Advances, vol. 12, no. 32,
AAAS, 2026, p. eadw5487, doi:10.1126/sciadv.adw5487.
short: I. Varela Martínez, A. Villalba Requena, J. García-Marqués, A. Aguilera,
D.S. Castro, S. Hippenmeyer, M. Nieto, Science Advances 12 (2026) eadw5487.
das_tickbox: '1'
dataavailabilitystatement: 'All data and code needed to evaluate and reproduce the
results in the paper are present in the paper and/or the Supplementary Materials.
Source data underlying all figures (including the clonal atlas) are provided in
the Supplementary Materials. RnA-seq analysis code has been deposited in Zenodo
(dOi: 10.5281/zenodo.14609057). this study did not generate new materials.'
date_created: 2026-08-16T22:01:43Z
date_published: 2026-08-07T00:00:00Z
date_updated: 2026-08-20T05:45:28Z
day: '07'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1126/sciadv.adw5487
external_id:
pmid:
- '42555737'
file:
- access_level: open_access
checksum: 487c3703387080e8f3c4675d67763f0e
content_type: application/pdf
creator: dernst
date_created: 2026-08-20T05:39:32Z
date_updated: 2026-08-20T05:39:32Z
file_id: '22738'
file_name: 2026_ScienceAdv_VarelaMartinez.pdf
file_size: 3056744
relation: main_file
success: 1
file_date_updated: 2026-08-20T05:39:32Z
fulldoi: https://doi.org/10.1126/sciadv.adw5487
has_accepted_license: '1'
intvolume: ' 12'
issue: '32'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: eadw5487
pmid: 1
publication: Science Advances
publication_identifier:
eissn:
- 2375-2548
publication_status: published
publisher: AAAS
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Early fate diversification of radial glial progenitors during corticogenesis
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: 12
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '22753'
abstract:
- lang: eng
text: Radial glial progenitors (RGPs) produce all excitatory neurons in the developing
cerebral cortex. Mosaic analysis with double markers (MADM)-based lineage tracing
in vivo has revealed a quantitative framework of RGP lineage progression1. Here
we established MADM technology2,3 in mouse embryonic stem cells to probe RGP lineage
progression in a self-organizing cortical organoid system. We found that RGPs
exhibit a high level of plasticity in proliferative potential in organoids rather
than strict temporally stereotyped lineage progression as observed in vivo. RGPs
in organoids showed increased lineage restriction, diminishing cell-type diversity
in clones of cortical projection neurons, despite uniform single-cell transcriptional
signatures of RGPs and a unitary lineage trajectory. Thus, critical non-cell-autonomous
cues that are absent in self-organizing systems and/or the genuine stem cell niche
are essential for faithful temporal control of RGP lineage progression and the
generation of clonal cortical cell-type diversity.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: We thank M. L. de Guevara, S. Jayaram and A. Heger for technical
assistance with mESC derivation; M. Goudarzi for assistance with organoid imaging;
M. Leeb and F. Freeman for advice in culturing mESCs and organoids; S. Gobeil and
L. Sweeney for reagents and advice for organoid clearing; A. Heger for mouse colony
management; J. Hauser for technical assistance; the Stanford Brain Organogenesis
Workshop; and all members of the Hippenmeyer laboratory for discussion and/or comments
on the manuscript. This study was supported by the Scientific Service Units (SSU)
of the Institute of Science and Technology, Austria through resources provided by
the Imaging and Optics Facility (IOF), Laboratory Support Facility (LSF) and Preclinical
Facility (PCF). M.S. received funding from the European Commission (IST plus postdoctoral
fellowship). This work was supported by ISTA institutional funds to S.H., FWF SFB
F78 Neuro Stem Modulation to S.H., 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. Open access funding provided by Institute of Science and
Technology (IST Austria).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Melissa A
full_name: Stouffer, Melissa A
id: 4C9372C4-F248-11E8-B48F-1D18A9856A87
last_name: Stouffer
- first_name: Osvaldo
full_name: Miranda, Osvaldo
id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
last_name: Miranda
orcid: 0000-0001-6618-6889
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Fabrizia
full_name: Pipicelli, Fabrizia
id: 649134fd-d012-11ed-8f82-db1e5050f9ba
last_name: Pipicelli
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- 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: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Stouffer MA, Miranda O, Pauler F, et al. Temporal uncoupling of radial glia
lineage progression in cortical organoids. Nature. 2026. doi:10.1038/s41586-026-10916-7
apa: Stouffer, M. A., Miranda, O., Pauler, F., Pipicelli, F., Streicher, C., Cheung,
G. T., & Hippenmeyer, S. (2026). Temporal uncoupling of radial glia lineage
progression in cortical organoids. Nature. Springer Nature. https://doi.org/10.1038/s41586-026-10916-7
chicago: Stouffer, Melissa A, Osvaldo Miranda, Florian Pauler, Fabrizia Pipicelli,
Carmen Streicher, Giselle T Cheung, and Simon Hippenmeyer. “Temporal Uncoupling
of Radial Glia Lineage Progression in Cortical Organoids.” Nature. Springer
Nature, 2026. https://doi.org/10.1038/s41586-026-10916-7.
ieee: M. A. Stouffer et al., “Temporal uncoupling of radial glia lineage
progression in cortical organoids,” Nature. Springer Nature, 2026.
ista: Stouffer MA, Miranda O, Pauler F, Pipicelli F, Streicher C, Cheung GT, Hippenmeyer
S. 2026. Temporal uncoupling of radial glia lineage progression in cortical organoids.
Nature.
mla: Stouffer, Melissa A., et al. “Temporal Uncoupling of Radial Glia Lineage Progression
in Cortical Organoids.” Nature, Springer Nature, 2026, doi:10.1038/s41586-026-10916-7.
short: M.A. Stouffer, O. Miranda, F. Pauler, F. Pipicelli, C. Streicher, G.T. Cheung,
S. Hippenmeyer, Nature (2026).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: All data generated and analysed in this study are included
in the paper, source data and/or Supplementary Tables 2 and 3. Raw sequencing data
have been deposited with Gene Expression Omnibus (GEO) accession number GSE327470.
Source data are provided with this paper. All scripts used to prepare data and figures
for this manuscript are accessible on GitHub at https://github.com/fpauler/Temporal-Uncoupling-of-Radial-Glia-Lineage-Progression-in-Cortical-Organoid.
date_created: 2026-08-23T22:01:47Z
date_published: 2026-08-12T00:00:00Z
date_updated: 2026-09-09T07:11:02Z
day: '12'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41586-026-10916-7
ec_funded: 1
external_id:
pmid:
- '42587153'
file:
- access_level: open_access
checksum: 11383e28fc430b28d2666f73833e8b56
content_type: application/pdf
creator: dernst
date_created: 2026-09-07T13:24:10Z
date_updated: 2026-09-07T13:24:10Z
file_id: '22844'
file_name: 2026_Nature_Stouffer.pdf
file_size: 48513068
relation: main_file
success: 1
file_date_updated: 2026-09-07T13:24:10Z
fulldoi: https://doi.org/10.1038/s41586-026-10916-7
has_accepted_license: '1'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
- _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: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: epub_ahead
publisher: Springer Nature
quality_controlled: '1'
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Temporal uncoupling of radial glia lineage progression in cortical organoids
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
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '21948'
abstract:
- lang: eng
text: The cerebral cortex comprises diverse neuron and glial cell types generated
by radial glial progenitors (RGPs) during development. Although RGPs broadly differentiate
according to temporally and spatially regulated molecular logics, the lineage
hierarchies linking individual progenitors to defined cell (sub)types are not
well understood. Clone-resolved transcriptomics, combining molecular barcoding
and single-cell RNA sequencing, allow high-resolution lineage tracing at the single-clone/cell
level across different species and models. In this mini-review, we synthesize
recent advances in this field, uncovering unexpected lineage relationships in
the developing brain, with a particular focus on the cerebral cortex. We further
highlight new insights into species-specific differences in the developmental
programs generating cell-type diversity, linking changes in clonal architecture
to lineage diversification during cortical evolution.
acknowledgement: We wish to thank all members of the Hippenmeyer laboratory at ISTA
for exciting discussions on the subject of this review. We apologize to colleagues
whose work we could not cite and/or discuss in the frame of the available space.
Work in the Hippenmeyer laboratory on the discussed topic is supported by ISTA institutional
funds, an EMBO LTF (ALTF 994–2023) to F.P., FWF SFB F78 (10.55776/F78) to S.H.,
and FWF Cluster of Excellence COE16 (10.55776/COE16) to S.H.
article_number: '102487'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Irene
full_name: Varela Martínez, Irene
id: a69b5985-8829-11f0-8fc2-d0af58f64471
last_name: Varela Martínez
- first_name: Fabrizia
full_name: Pipicelli, Fabrizia
id: 649134fd-d012-11ed-8f82-db1e5050f9ba
last_name: Pipicelli
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: 'Varela Martínez I, Pipicelli F, Hippenmeyer S. Tracing cell lineages in the
developing brain: Insights from mosaic analysis and clone-resolved transcriptomics.
Current Opinion in Genetics & Development. 2026;99. doi:10.1016/j.gde.2026.102487'
apa: 'Varela Martínez, I., Pipicelli, F., & Hippenmeyer, S. (2026). Tracing
cell lineages in the developing brain: Insights from mosaic analysis and clone-resolved
transcriptomics. Current Opinion in Genetics & Development. Elsevier.
https://doi.org/10.1016/j.gde.2026.102487'
chicago: 'Varela Martínez, Irene, Fabrizia Pipicelli, and Simon Hippenmeyer. “Tracing
Cell Lineages in the Developing Brain: Insights from Mosaic Analysis and Clone-Resolved
Transcriptomics.” Current Opinion in Genetics & Development. Elsevier,
2026. https://doi.org/10.1016/j.gde.2026.102487.'
ieee: 'I. Varela Martínez, F. Pipicelli, and S. Hippenmeyer, “Tracing cell lineages
in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics,”
Current Opinion in Genetics & Development, vol. 99. Elsevier, 2026.'
ista: 'Varela Martínez I, Pipicelli F, Hippenmeyer S. 2026. Tracing cell lineages
in the developing brain: Insights from mosaic analysis and clone-resolved transcriptomics.
Current Opinion in Genetics & Development. 99, 102487.'
mla: 'Varela Martínez, Irene, et al. “Tracing Cell Lineages in the Developing Brain:
Insights from Mosaic Analysis and Clone-Resolved Transcriptomics.” Current
Opinion in Genetics & Development, vol. 99, 102487, Elsevier, 2026, doi:10.1016/j.gde.2026.102487.'
short: I. Varela Martínez, F. Pipicelli, S. Hippenmeyer, Current Opinion in Genetics
& Development 99 (2026).
corr_author: '1'
date_created: 2026-06-07T22:01:35Z
date_published: 2026-05-29T00:00:00Z
date_updated: 2026-09-16T07:34:44Z
day: '29'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.gde.2026.102487
external_id:
pmid:
- '42214837'
fulldoi: https://doi.org/10.1016/j.gde.2026.102487
has_accepted_license: '1'
intvolume: ' 99'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.gde.2026.102487
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 7c084566-9f16-11ee-852c-c88a1dbbf1cf
grant_number: ALTF 994-2023
name: Role of cell lineage in generating cell-type diversity in developing neocortex’
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
- _id: 9e227eae-b037-11f1-b1e2-fb7da760c1dd
grant_number: COE16
name: Neuronal circuits in health and disease (Hippenmeyer)
publication: Current Opinion in Genetics & Development
publication_identifier:
eissn:
- 1879-0380
issn:
- 0959-437X
publication_status: epub_ahead
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Tracing cell lineages in the developing brain: Insights from mosaic analysis
and clone-resolved transcriptomics'
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: 99
year: '2026'
...
---
OA_place: repository
OA_type: green
_id: '23011'
abstract:
- lang: eng
text: "Alternative splicing represents a major source of potential evolutionary
novelty in protein sequence. Despite this, relatively few studies have investigated
the functional impacts of human-specific alternative splicing. Here, we analyze
RNA-sequencing data from nine iPSC-derived cell types and identify dozens of human
transcriptomic conserved deletions (htCONDELs): evolutionary divergence in splicing
that leads to the partial or full removal of conserved protein-coding sequence
from the human transcriptome. We investigated one example in detail: an htCONDEL
in the gene\r\nHMMR\r\n , which encodes a centrosomal protein
that binds microtubules and regulates mitosis. We found that this htCONDEL, which
produces a human-specific isoform lacking a conserved microtubule-binding domain,
enables cells to flexibly divide with a broader range of mitotic spindle orientations\r\n
\ in vitro\r\n . Introducing the human\r\n HMMR\r\n
\ isoform into mice similarly alters the orientation of cell division
in the developing neocortex and increases the production of outer radial glia-like
cells, the expansion of which played an essential role in increasing human brain
size. Combined with previous work implicating the same\r\n HMMR\r\n
\ isoform in carcinoma progression, our results suggest that evolution
of\r\nHMMR\r\n splicing in humans increased plasticity in cell
division, potentially leading to tradeoffs between advantageous effects on brain
development and deleterious effects on cancer risk later in life."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
acknowledgement: "We would like to acknowledge the MSKCC transgenic mouse core facility
for generating\r\nhumanized mice, as well as Nancy Du, Xiang Chen, and other Du
lab members for mouse\r\nbreeding and genotyping. This research was supported by
the Scientific Service Units (SSU) of\r\nIST Austria through resources provided
by the Imaging and Optics- (IOF), Lab Support- (LSF)\r\nand Preclinical Facilities
(PCF). We would also like to thank Fee Wielath and Kerstin Feistel for\r\nhelpful
discussions. Some figures were made with biorender. Work in the Fraser laboratory
is supported by NIH grants R01HG012285 and R35GM156526.\r\nWork in the Hippenmeyer
laboratory is supported by ISTA institutional funds and FWF Cluster of\r\nExcellence
COE16 (10.55776/COE16) to S.H. Work in the Maxwell laboratory is supported by\r\nthe
National Sciences and Engineering Research Council of Canada (NSERC, RGPIN-2019-\r\n06215
and 2025-05766) and the Canadian Institutes of Health Research (F24-00975). J.R.
is\r\nsupported by a Canada Graduate Research Scholarship-Doctoral (612468 - 2026)
from\r\nNSERC. A.L.S. is supported by the FutureHouse postdoctoral fellowship program
and the Kavli\r\nFoundation. "
article_processing_charge: No
author:
- first_name: Alexander L.
full_name: Starr, Alexander L.
last_name: Starr
- first_name: Ana
full_name: Villalba Requena, Ana
id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
last_name: Villalba Requena
orcid: 0000-0002-5615-5277
- first_name: Jenna
full_name: Rever, Jenna
last_name: Rever
- first_name: Yuwei
full_name: Chen, Yuwei
id: 7f9e985d-7380-11f0-bf20-b4121a7bdcbc
last_name: Chen
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Leslie
full_name: Magtanong, Leslie
last_name: Magtanong
- first_name: Christopher A.
full_name: Maxwell, Christopher A.
last_name: Maxwell
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Hunter B.
full_name: Fraser, Hunter B.
last_name: Fraser
biorxivid: 1
citation:
ama: Starr AL, Villalba Requena A, Rever J, et al. A human transcriptomic deletion
links cortical expansion and cancer. bioRxiv. doi:10.64898/2026.09.16.752114
apa: Starr, A. L., Villalba Requena, A., Rever, J., Chen, Y., Pauler, F., Magtanong,
L., … Fraser, H. B. (n.d.). A human transcriptomic deletion links cortical expansion
and cancer. bioRxiv. https://doi.org/10.64898/2026.09.16.752114
chicago: Starr, Alexander L., Ana Villalba Requena, Jenna Rever, Yuwei Chen, Florian
Pauler, Leslie Magtanong, Christopher A. Maxwell, Simon Hippenmeyer, and Hunter
B. Fraser. “A Human Transcriptomic Deletion Links Cortical Expansion and Cancer.”
BioRxiv, n.d. https://doi.org/10.64898/2026.09.16.752114.
ieee: A. L. Starr et al., “A human transcriptomic deletion links cortical
expansion and cancer,” bioRxiv. .
ista: Starr AL, Villalba Requena A, Rever J, Chen Y, Pauler F, Magtanong L, Maxwell
CA, Hippenmeyer S, Fraser HB. A human transcriptomic deletion links cortical expansion
and cancer. bioRxiv, 10.64898/2026.09.16.752114.
mla: Starr, Alexander L., et al. “A Human Transcriptomic Deletion Links Cortical
Expansion and Cancer.” BioRxiv, doi:10.64898/2026.09.16.752114.
short: A.L. Starr, A. Villalba Requena, J. Rever, Y. Chen, F. Pauler, L. Magtanong,
C.A. Maxwell, S. Hippenmeyer, H.B. Fraser, BioRxiv (n.d.).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: "Bulk and single cell RNA-sequencing data generated in
this study have been uploaded to the\r\nGene expression omnibus (GEO) with accessions
GSE346330 and GSE346338 respectively. \r\nBulk RNA-seq data used to identify htCONDELs
are publicly available with the following GEO\r\naccessions: GSE146481, GSE144825,
and GSE232949. Splicing data from additional species\r\nwas downloaded from https://apps.kaessmannlab.org/alternative-splicing/
and GTEx v10 sQTL\r\ndata was downloaded from https://gtexportal.org/api/v2/association/dynsqtl.\r\nCode
for this study is available at: https://github.com/astarr97/Splicing. Code to perform
the\r\nalignment of RNA-seq data from hybrid cells is available at: https://github.com/banwang27/multi1216
celltypes. "
date_created: 2026-10-01T07:21:25Z
date_published: 2026-09-18T00:00:00Z
date_updated: 2026-10-07T08:50:37Z
day: '18'
department:
- _id: SiHi
doi: 10.64898/2026.09.16.752114
external_id:
biorxivid:
- 10.64898/2026.09.16.752114
fulldoi: https://doi.org/10.64898/2026.09.16.752114
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.64898/2026.09.16.752114
month: '09'
oa: 1
oa_version: Preprint
project:
- _id: 9e227eae-b037-11f1-b1e2-fb7da760c1dd
grant_number: COE16
name: Neuronal circuits in health and disease (Hippenmeyer)
publication: bioRxiv
publication_status: submitted
researchdata_availability: yes
status: public
supplementarymaterial: yes
title: A human transcriptomic deletion links cortical expansion and cancer
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2026'
...
---
OA_place: publisher
OA_type: gold
_id: '14647'
abstract:
- lang: eng
text: "In the developing vertebrate central nervous system, neurons and glia typically
arise\r\nsequentially from common progenitors. Here, we report that the transcription
factor Forkhead\r\nBox G1 (Foxg1) regulates gliogenesis in the mouse neocortex
via distinct cell-autonomous roles in progenitors and postmitotic neurons that
regulate different aspects of the gliogenic FGF signalling pathway. We demonstrate
that loss of Foxg1 in cortical progenitors at neurogenic stages causes premature
astrogliogenesis. We identify a novel FOXG1 target, the pro-gliogenic FGF pathway
component Fgfr3, which is suppressed by FOXG1 cell-autonomously to maintain neurogenesis.
Furthermore, FOXG1 can also suppress premature astrogliogenesis triggered by the
augmentation of FGF signalling. We identify a second novel function of FOXG1 in
regulating the expression of gliogenic cues in newborn neocortical upper-layer
neurons. Loss of FOXG1 in postmitotic neurons non-autonomously enhances gliogenesis
in the progenitors via FGF signalling. These results fit well with the model that
newborn neurons secrete cues that trigger progenitors to produce the next wave
of cell types, astrocytes. If FGF signalling is attenuated in Foxg1 null progenitors,
they progress to oligodendrocyte production. Therefore, loss of FOXG1 transitions
the progenitor to a gliogenic state, producing either astrocytes or oligodendrocytes
depending on FGF signalling levels. Our results uncover how FOXG1 integrates extrinsic
signalling via the FGF pathway to regulate the sequential generation of neurons,
astrocytes, and oligodendrocytes in the cerebral cortex. "
acknowledgement: "We thank the animal house staff of the Tata Institute of Fundamental
Research, Mumbai (TIFR), for their excellent support; Gordon Fishell (Harvard Medical
School, USA), and Goichi Miyoshi (Gunma University, Japan) for the Foxg1 floxed
mouse line; Hiroshi Kawasaki (Kanazawa University, Japan) for the plasmids pCAG-FGF8
and pCAG-sFgfr3c; Soo Kyung Lee (University at Buffalo, The State University of
New York, USA) for the Foxg1lox/lox genotyping primers and protocol. We thank Deepak
Modi and Vainav Patel (National Institute for Research in Reproductive and Child
Health, NIRRCH, Mumbai, India) for the use of the NIRRCH FACS Facility, and the
staff of the NIRRCH and TIFR FACS facilities for their assistance. We thank Denis
Jabaudon (University of Geneva, Switzerland) for his critical comments on the manuscript
and members of the Jabaudon lab for helpful discussions. This work was funded by
the Department of Atomic Energy (DAE), Govt. of India (Project Identification no.
RTI4003,\r\nDAE OM no. 1303/2/2019/R&D-II/DAE/2079). "
article_number: '101851'
article_processing_charge: Yes
article_type: original
author:
- first_name: Mahima
full_name: Bose, Mahima
last_name: Bose
- first_name: Varun
full_name: Suresh, Varun
last_name: Suresh
- first_name: Urvi
full_name: Mishra, Urvi
last_name: Mishra
- first_name: Ishita
full_name: Talwar, Ishita
last_name: Talwar
- first_name: Anuradha
full_name: Yadav, Anuradha
last_name: Yadav
- first_name: Shiona
full_name: Biswas, Shiona
last_name: Biswas
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Shubha
full_name: Tole, Shubha
last_name: Tole
citation:
ama: Bose M, Suresh V, Mishra U, et al. Dual role of FOXG1 in regulating gliogenesis
in the developing neocortex via the FGF signalling pathway. eLife. 2025;13.
doi:10.7554/elife.101851.3
apa: Bose, M., Suresh, V., Mishra, U., Talwar, I., Yadav, A., Biswas, S., … Tole,
S. (2025). Dual role of FOXG1 in regulating gliogenesis in the developing neocortex
via the FGF signalling pathway. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.101851.3
chicago: Bose, Mahima, Varun Suresh, Urvi Mishra, Ishita Talwar, Anuradha Yadav,
Shiona Biswas, Simon Hippenmeyer, and Shubha Tole. “Dual Role of FOXG1 in Regulating
Gliogenesis in the Developing Neocortex via the FGF Signalling Pathway.” ELife.
eLife Sciences Publications, 2025. https://doi.org/10.7554/elife.101851.3.
ieee: M. Bose et al., “Dual role of FOXG1 in regulating gliogenesis in the
developing neocortex via the FGF signalling pathway,” eLife, vol. 13. eLife
Sciences Publications, 2025.
ista: Bose M, Suresh V, Mishra U, Talwar I, Yadav A, Biswas S, Hippenmeyer S, Tole
S. 2025. Dual role of FOXG1 in regulating gliogenesis in the developing neocortex
via the FGF signalling pathway. eLife. 13, 101851.
mla: Bose, Mahima, et al. “Dual Role of FOXG1 in Regulating Gliogenesis in the Developing
Neocortex via the FGF Signalling Pathway.” ELife, vol. 13, 101851, eLife
Sciences Publications, 2025, doi:10.7554/elife.101851.3.
short: M. Bose, V. Suresh, U. Mishra, I. Talwar, A. Yadav, S. Biswas, S. Hippenmeyer,
S. Tole, ELife 13 (2025).
date_created: 2023-12-06T13:07:01Z
date_published: 2025-03-14T00:00:00Z
date_updated: 2025-05-14T11:41:52Z
day: '14'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.7554/elife.101851.3
external_id:
pmid:
- '40085500'
file:
- access_level: open_access
checksum: 64a6a6f86e24b21fe72c7a7fd6056fed
content_type: application/pdf
creator: dernst
date_created: 2025-04-03T11:19:26Z
date_updated: 2025-04-03T11:19:26Z
file_id: '19467'
file_name: 2025_eLife_Bose.pdf
file_size: 17462771
relation: main_file
success: 1
file_date_updated: 2025-04-03T11:19:26Z
fulldoi: https://doi.org/10.7554/elife.101851.3
has_accepted_license: '1'
intvolume: ' 13'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via
the FGF signalling pathway
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: '2025'
...
---
OA_type: closed access
_id: '18765'
abstract:
- lang: eng
text: Mosaic Analysis with Double Markers (MADM) represents a mouse genetic approach
coupling differential fluorescent labeling to genetic manipulations in dividing
cells and their lineages. MADM uniquely enables the generation and visualization
of individual control or homozygous mutant cells in a heterozygous genetic environment.
Among its diverse applications, MADM has been used to dissect cell-autonomous
gene functions important for cortical development and neural development in general.
The high cellular resolution offered by MADM also permits the analysis of transcriptomic
changes of individual cells upon genetic manipulations. In this chapter, we describe
an experimental protocol combining the generation and isolation of MADM-labeled
cells with downstream single-cell RNA-sequencing technologies to probe cell-type
specific phenotypes due to genetic mutations at single-cell resolution.
acknowledged_ssus:
- _id: Bio
acknowledgement: 'We thank all Hippenmeyer lab members for support and discussions.
Experimental steps described were optimized with support provided by the Imaging
& Optics Facility (IOF) and Preclinical Facility (PCF) at ISTA, Vienna BioCenter
Core Facilities (VBCF), and Christoph Bock lab at Center for Molecular Medicine
(CeMM). G.C. received funding from European Commission (IST plus postdoctoral fellowship).
This work was supported by ISTA institutional funds: The Austrian Science Fund Special
Research Programmes (FWF SFB F78 Neuro Stem Modulation) to S.H.'
alternative_title:
- Methods in Molecular Biology
article_processing_charge: No
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: 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
citation:
ama: 'Cheung GT, Pauler F, Hippenmeyer S. Probing Cell-Type Specificity of Mutant
Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM).
In: Garcia-Marques J, Lee T, eds. Lineage Tracing. Vol 2886. MIMB. New
York, NY: Springer Nature; 2025:139-151. doi:10.1007/978-1-0716-4310-5_7'
apa: 'Cheung, G. T., Pauler, F., & Hippenmeyer, S. (2025). Probing Cell-Type
Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis
with Double Markers (MADM). In J. Garcia-Marques & T. Lee (Eds.), Lineage
Tracing (Vol. 2886, pp. 139–151). New York, NY: Springer Nature. https://doi.org/10.1007/978-1-0716-4310-5_7'
chicago: 'Cheung, Giselle T, Florian Pauler, and Simon Hippenmeyer. “Probing Cell-Type
Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis
with Double Markers (MADM).” In Lineage Tracing, edited by Jorge Garcia-Marques
and Tzumin Lee, 2886:139–51. MIMB. New York, NY: Springer Nature, 2025. https://doi.org/10.1007/978-1-0716-4310-5_7.'
ieee: 'G. T. Cheung, F. Pauler, and S. Hippenmeyer, “Probing Cell-Type Specificity
of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double
Markers (MADM),” in Lineage Tracing, vol. 2886, J. Garcia-Marques and T.
Lee, Eds. New York, NY: Springer Nature, 2025, pp. 139–151.'
ista: 'Cheung GT, Pauler F, Hippenmeyer S. 2025.Probing Cell-Type Specificity of
Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers
(MADM). In: Lineage Tracing. Methods in Molecular Biology, vol. 2886, 139–151.'
mla: Cheung, Giselle T., et al. “Probing Cell-Type Specificity of Mutant Phenotype
at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM).” Lineage
Tracing, edited by Jorge Garcia-Marques and Tzumin Lee, vol. 2886, Springer
Nature, 2025, pp. 139–51, doi:10.1007/978-1-0716-4310-5_7.
short: G.T. Cheung, F. Pauler, S. Hippenmeyer, in:, J. Garcia-Marques, T. Lee (Eds.),
Lineage Tracing, Springer Nature, New York, NY, 2025, pp. 139–151.
corr_author: '1'
date_created: 2025-01-07T08:36:47Z
date_published: 2025-01-03T00:00:00Z
date_updated: 2025-04-14T07:43:46Z
day: '03'
department:
- _id: SiHi
doi: 10.1007/978-1-0716-4310-5_7
ec_funded: 1
editor:
- first_name: Jorge
full_name: Garcia-Marques, Jorge
last_name: Garcia-Marques
- first_name: Tzumin
full_name: Lee, Tzumin
last_name: Lee
external_id:
pmid:
- '39745639'
fulldoi: https://doi.org/10.1007/978-1-0716-4310-5_7
intvolume: ' 2886'
language:
- iso: eng
month: '01'
oa_version: None
page: 139-151
place: New York, NY
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Lineage Tracing
publication_identifier:
eisbn:
- '9781071643105'
eissn:
- 1940-6029
isbn:
- '9781071643099'
issn:
- 1064-3745
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
series_title: MIMB
status: public
title: Probing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using
Mosaic Analysis with Double Markers (MADM)
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 2886
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '19718'
abstract:
- lang: eng
text: The cerebral cortex is arguably the most complex organ in humans. The cortical
architecture is characterized by a remarkable diversity of neuronal and glial
cell types that make up its neuronal circuits. Following a precise temporally
ordered program, radial glia progenitor (RGP) cells generate all cortical excitatory
projection neurons and glial cell-types. Cortical excitatory projection neurons
are produced either directly or via intermediate progenitors, through indirect
neurogenesis. How the extensive cortical cell-type diversity is generated during
cortex development remains, however, a fundamental open question. How do RGPs
quantitatively and qualitatively generate all the neocortical neurons? How does
direct and indirect neurogenesis contribute to the establishment of neuronal and
lineage heterogeneity? Whether RGPs represent a homogeneous and/or multipotent
progenitor population, or if RGPs consist of heterogeneous groups is currently
also not known. In this review, we will summarize the latest findings that contributed
to a deeper insight into the above key questions.
acknowledgement: We wish to thank all members of the Hippenmeyer laboratory at ISTA
for exciting discussions on the subject of this review. We apologize to colleagues
whose work we could not cite and/or discuss in the frame of the available space.
Work in the Hippenmeyer laboratory on the discussed topic is supported by ISTA institutional
funds, an EMBO LTF (ALTF 994–2023) to F.P, and FWF SFB F78 to S.H.
article_number: '103046'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Fabrizia
full_name: Pipicelli, Fabrizia
id: 649134fd-d012-11ed-8f82-db1e5050f9ba
last_name: Pipicelli
- first_name: Ana
full_name: Villalba Requena, Ana
id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
last_name: Villalba Requena
orcid: 0000-0002-5615-5277
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Pipicelli F, Villalba Requena A, Hippenmeyer S. How radial glia progenitor
lineages generate cell-type diversity in the developing cerebral cortex. Current
Opinion in Neurobiology. 2025;93. doi:10.1016/j.conb.2025.103046
apa: Pipicelli, F., Villalba Requena, A., & Hippenmeyer, S. (2025). How radial
glia progenitor lineages generate cell-type diversity in the developing cerebral
cortex. Current Opinion in Neurobiology. Elsevier. https://doi.org/10.1016/j.conb.2025.103046
chicago: Pipicelli, Fabrizia, Ana Villalba Requena, and Simon Hippenmeyer. “How
Radial Glia Progenitor Lineages Generate Cell-Type Diversity in the Developing
Cerebral Cortex.” Current Opinion in Neurobiology. Elsevier, 2025. https://doi.org/10.1016/j.conb.2025.103046.
ieee: F. Pipicelli, A. Villalba Requena, and S. Hippenmeyer, “How radial glia progenitor
lineages generate cell-type diversity in the developing cerebral cortex,” Current
Opinion in Neurobiology, vol. 93. Elsevier, 2025.
ista: Pipicelli F, Villalba Requena A, Hippenmeyer S. 2025. How radial glia progenitor
lineages generate cell-type diversity in the developing cerebral cortex. Current
Opinion in Neurobiology. 93, 103046.
mla: Pipicelli, Fabrizia, et al. “How Radial Glia Progenitor Lineages Generate Cell-Type
Diversity in the Developing Cerebral Cortex.” Current Opinion in Neurobiology,
vol. 93, 103046, Elsevier, 2025, doi:10.1016/j.conb.2025.103046.
short: F. Pipicelli, A. Villalba Requena, S. Hippenmeyer, Current Opinion in Neurobiology
93 (2025).
corr_author: '1'
date_created: 2025-05-20T10:20:09Z
date_published: 2025-08-01T00:00:00Z
date_updated: 2025-12-30T10:54:14Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1016/j.conb.2025.103046
external_id:
isi:
- '001496227000001'
pmid:
- '40383049'
file:
- access_level: open_access
checksum: 05bacb4acbe6275d43e873dec9ba1d52
content_type: application/pdf
creator: dernst
date_created: 2025-12-30T08:25:49Z
date_updated: 2025-12-30T08:25:49Z
file_id: '20894'
file_name: 2025_CurrentOpNeurobiology_Pipicelli.pdf
file_size: 1592649
relation: main_file
success: 1
file_date_updated: 2025-12-30T08:25:49Z
fulldoi: https://doi.org/10.1016/j.conb.2025.103046
has_accepted_license: '1'
intvolume: ' 93'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
- _id: 7c084566-9f16-11ee-852c-c88a1dbbf1cf
grant_number: ALTF 994-2023
name: Role of cell lineage in generating cell-type diversity in developing neocortex’
publication: Current Opinion in Neurobiology
publication_identifier:
issn:
- 0959-4388
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: How radial glia progenitor lineages generate cell-type diversity in the developing
cerebral cortex
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: 93
year: '2025'
...
---
OA_type: closed access
_id: '20079'
abstract:
- lang: eng
text: "Research question: Is LINC01638 involved in regulation of epithelial-to-mesenchymal
transition (EMT) in endometriosis?\r\nDesign: A prospective patient cohort study
was combined with functional experiments in the 12Z endometriosis epithelial cell
line to investigate the role of LINC01638 in endometriosis. Eutopic endometrial
samples were collected by curettage, and ectopic endometrial lesion samples were
collected by laparoscopic surgery from 24 control patients and 41 patients with
endometriosis. The phenotype of 12Z cells was assessed following LINC01638 knockdown
using siRNA, performing proliferation, adhesion, migration and invasion assays,
as well as assessing apoptosis and cell cycle changes with flow cytometry assays.
In order to assess the relationship between LINC01638 and histone deacetylase
class 1 enzyme (HDAC1), LINC01638 knockdown was combined with HDAC inhibition
with the specific HDAC inhibitor romidepsin.\r\nResults: LINC01638 was up-regulated
in the epithelial layer of endometriotic lesions, and LINC01638 knockdown in 12Z
cells led to reduced proliferation, adhesion, migration and invasion. The reduction
in proliferation was associated with increased p21 and p27 expression, and G1
phase arrest. Further analysis of LINC01638 control and knockdown cells revealed
that a number of transcription factors associated with EMT are down-regulated
in knockdown cells, along with the cytoskeleton regulatory gene RHOB, while HDAC1
was up-regulated. Chromatin immunoprecipitation analysis and HDAC1 inhibitory
treatment combined with LINC01638 knockdown indicated that LINC01638 regulates
RHOB expression via HDAC1-mediated promoter deacetylation. RHOB is up-regulated
in the epithelial layer of endometriotic lesions compared with eutopic endometrium,
supporting a role in the disease.\r\nConclusions: LINC01638 is an epigenetic regulator
of the pathogenesis of endometriosis, promoting proliferation and EMT of endometriotic
lesions."
acknowledgement: "The authors wish to thank all the participants and health professionals
involved in this study. In addition, the authors wish to thank technical assistants
Barbara Widmar, Matthias Witzmann-Stern and Isabella Haslinger for their work assisting
with this study; and Simon Hippenmeyer for access to bioinformatic infrastructure
and resources.\r\nOpen access funding was provided by the Medical University of
Vienna."
article_number: '104942'
article_processing_charge: No
article_type: original
author:
- first_name: Iveta
full_name: Yotova, Iveta
last_name: Yotova
- first_name: Katharina
full_name: Proestling, Katharina
last_name: Proestling
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Lisa
full_name: Rainer, Lisa
last_name: Rainer
- first_name: Leonie
full_name: Kaup, Leonie
last_name: Kaup
- first_name: Jana
full_name: Heine, Jana
last_name: Heine
- first_name: Lejla
full_name: Sandrieser, Lejla
last_name: Sandrieser
- first_name: René
full_name: Wenzl, René
last_name: Wenzl
- first_name: Quanah J.
full_name: Hudson, Quanah J.
last_name: Hudson
citation:
ama: Yotova I, Proestling K, Pauler F, et al. LINC01638 promotes epithelial-to-mesenchymal
transition in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression.
Reproductive Biomedicine Online. 2025;51(3). doi:10.1016/j.rbmo.2025.104942
apa: Yotova, I., Proestling, K., Pauler, F., Rainer, L., Kaup, L., Heine, J., …
Hudson, Q. J. (2025). LINC01638 promotes epithelial-to-mesenchymal transition
in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression.
Reproductive Biomedicine Online. Elsevier. https://doi.org/10.1016/j.rbmo.2025.104942
chicago: Yotova, Iveta, Katharina Proestling, Florian Pauler, Lisa Rainer, Leonie
Kaup, Jana Heine, Lejla Sandrieser, René Wenzl, and Quanah J. Hudson. “LINC01638
Promotes Epithelial-to-Mesenchymal Transition in Endometriosis Epithelial Cells
by up-Regulating RHOB via HDAC1 Suppression.” Reproductive Biomedicine Online.
Elsevier, 2025. https://doi.org/10.1016/j.rbmo.2025.104942.
ieee: I. Yotova et al., “LINC01638 promotes epithelial-to-mesenchymal transition
in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression,”
Reproductive Biomedicine Online, vol. 51, no. 3. Elsevier, 2025.
ista: Yotova I, Proestling K, Pauler F, Rainer L, Kaup L, Heine J, Sandrieser L,
Wenzl R, Hudson QJ. 2025. LINC01638 promotes epithelial-to-mesenchymal transition
in endometriosis epithelial cells by up-regulating RHOB via HDAC1 suppression.
Reproductive Biomedicine Online. 51(3), 104942.
mla: Yotova, Iveta, et al. “LINC01638 Promotes Epithelial-to-Mesenchymal Transition
in Endometriosis Epithelial Cells by up-Regulating RHOB via HDAC1 Suppression.”
Reproductive Biomedicine Online, vol. 51, no. 3, 104942, Elsevier, 2025,
doi:10.1016/j.rbmo.2025.104942.
short: I. Yotova, K. Proestling, F. Pauler, L. Rainer, L. Kaup, J. Heine, L. Sandrieser,
R. Wenzl, Q.J. Hudson, Reproductive Biomedicine Online 51 (2025).
date_created: 2025-07-27T22:01:25Z
date_published: 2025-07-17T00:00:00Z
date_updated: 2025-09-30T14:10:46Z
day: '17'
department:
- _id: SiHi
doi: 10.1016/j.rbmo.2025.104942
external_id:
isi:
- '001549819000002'
pmid:
- '40680553'
fulldoi: https://doi.org/10.1016/j.rbmo.2025.104942
intvolume: ' 51'
isi: 1
issue: '3'
language:
- iso: eng
month: '07'
oa_version: None
pmid: 1
publication: Reproductive Biomedicine Online
publication_identifier:
eissn:
- 1472-6491
issn:
- 1472-6483
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: LINC01638 promotes epithelial-to-mesenchymal transition in endometriosis epithelial
cells by up-regulating RHOB via HDAC1 suppression
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 51
year: '2025'
...
---
OA_place: publisher
_id: '20737'
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: "I also want to thank ISTA and the Austrian Science Fund FWF SFB
F78 (F7805) for financially\r\nsupporting my research."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Raquel
full_name: Casado Polanco, Raquel
id: 15240fc1-dbcd-11ea-9d1d-ac5a786425fd
last_name: Casado Polanco
orcid: 0000-0001-8293-4568
citation:
ama: Casado Polanco R. Role of NOTCH signaling in radial glial progenitor lineage
progression. 2025. doi:10.15479/AT-ISTA-20737
apa: Casado Polanco, R. (2025). Role of NOTCH signaling in radial glial progenitor
lineage progression. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20737
chicago: Casado Polanco, Raquel. “Role of NOTCH Signaling in Radial Glial Progenitor
Lineage Progression.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20737.
ieee: R. Casado Polanco, “Role of NOTCH signaling in radial glial progenitor lineage
progression,” Institute of Science and Technology Austria, 2025.
ista: Casado Polanco R. 2025. Role of NOTCH signaling in radial glial progenitor
lineage progression. Institute of Science and Technology Austria.
mla: Casado Polanco, Raquel. Role of NOTCH Signaling in Radial Glial Progenitor
Lineage Progression. Institute of Science and Technology Austria, 2025, doi:10.15479/AT-ISTA-20737.
short: R. Casado Polanco, Role of NOTCH Signaling in Radial Glial Progenitor Lineage
Progression, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-12-09T09:04:18Z
date_published: 2025-12-09T00:00:00Z
date_updated: 2026-04-14T08:16:58Z
day: '09'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SiHi
doi: 10.15479/AT-ISTA-20737
file:
- access_level: closed
checksum: 71e0fdf4619b0d70d03657ad7348137d
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: rcasadop
date_created: 2025-12-11T09:28:09Z
date_updated: 2025-12-11T11:18:37Z
file_id: '20793'
file_name: 2025_CasadoPolanco_Raquel_Thesis.docx
file_size: 78207207
relation: source_file
- access_level: closed
checksum: 58cf2f25c33567723bc754a019c3e396
content_type: application/pdf
creator: rcasadop
date_created: 2025-12-11T09:28:04Z
date_updated: 2025-12-11T09:28:04Z
embargo: 2026-12-01
embargo_to: open_access
file_id: '20794'
file_name: 2025_CasadoPolanco_Raquel_Thesis.pdf
file_size: 6261874
relation: main_file
file_date_updated: 2025-12-11T11:18:37Z
fulldoi: https://doi.org/10.15479/AT-ISTA-20737
has_accepted_license: '1'
keyword:
- NOTCH
- radial glial progenitor
- lineage progression
- cortical development
language:
- iso: eng
month: '12'
oa_version: Published Version
page: '133'
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
publication_identifier:
isbn:
- 978-3-99078-072-5
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
title: Role of NOTCH signaling in radial glial progenitor lineage progression
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '8616'
abstract:
- lang: eng
text: The brain vasculature supplies neurons with glucose and oxygen, but little
is known about how vascular plasticity contributes to brain function. Using longitudinal
in vivo imaging, we report that a substantial proportion of blood vessels in the
adult mouse brain sporadically occlude and regress. Their regression proceeds
through sequential stages of blood-flow occlusion, endothelial cell collapse,
relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels
are found to be widespread in mouse, monkey and human brains. We further reveal
that blood vessel regression cause a reduction of neuronal activity due to a dysfunction
in mitochondrial metabolism and glutamate production. Our results elucidate the
mechanism of vessel regression and its role in neuronal function in the adult
brain.
acknowledgement: 'The project was initiated in the Jan lab at UCSF. We thank Lily
Jan and Yuh-Nung Jan’s generous support. We thank Liqun Luo’s lab for providing
MADM-7 mice and Rolf A Brekken for VEGF-antibodies. Drs. Yuanquan Song (UPenn),
Zhaozhu Hu (JHU), Ji Hu (ShanghaiTech), Yang Xiang (U. Mass), Hao Wang (Zhejiang
U.) and Ruikang Wang (U. Washington) for critical input, colleagues at Children’s
Research Institute, Departments of Neuroscience, Neurology and Neurotherapeutics,
Pediatrics from UT Southwestern, and colleagues from the Jan lab for discussion.
Dr. Bridget Samuels, Sean Morrison (UT Southwestern), and Nannan Lu (Zhejiang U.)
for critical reading. We acknowledge the assistance of the CIBR Imaging core. We
also thank UT Southwestern Live Cell Imaging Facility, a Shared Resource of the
Harold C. Simmons Cancer Center, supported in part by an NCI Cancer Center Support
Grant, P30 CA142543K. This work is supported by CIBR funds and the American Heart
Association AWRP Summer 2016 Innovative Research Grant (17IRG33410377) to W-P.G.;
National Natural Science Foundation of China (No.81370031) to Z.Z.;National Key
Research and Development Program of China (2016YFE0125400)to F.H.;National Natural
Science Foundations of China (No. 81473202) to Y.L.; National Natural Science Foundation
of China (No.31600839) and Shenzhen Science and Technology Research Program (JCYJ20170818163320865)
to B.P.; National Natural Science Foundation of China (No. 31800864) and Westlake
University start-up funds to J-M. J. NIH R01NS088627 to W.L.J.; NIH: R01 AG020670
and RF1AG054111 to H.Z.; R01 NS088555 to A.M.S., and European Research Council No.725780
to S.H.;W-P.G. was a recipient of Bugher-American Heart Association Dan Adams Thinking
Outside the Box Award.'
article_number: '5840'
article_processing_charge: Yes
article_type: original
author:
- first_name: Xiaofei
full_name: Gao, Xiaofei
last_name: Gao
- first_name: Jun-Liszt
full_name: Li, Jun-Liszt
last_name: Li
- first_name: Xingjun
full_name: Chen, Xingjun
last_name: Chen
- first_name: Bo
full_name: Ci, Bo
last_name: Ci
- first_name: Fei
full_name: Chen, Fei
last_name: Chen
- first_name: Nannan
full_name: Lu, Nannan
last_name: Lu
- first_name: Bo
full_name: Shen, Bo
last_name: Shen
- first_name: Lijun
full_name: Zheng, Lijun
last_name: Zheng
- first_name: Jie-Min
full_name: Jia, Jie-Min
last_name: Jia
- first_name: Yating
full_name: Yi, Yating
last_name: Yi
- first_name: Shiwen
full_name: Zhang, Shiwen
last_name: Zhang
- first_name: Ying-Chao
full_name: Shi, Ying-Chao
last_name: Shi
- first_name: Kaibin
full_name: Shi, Kaibin
last_name: Shi
- first_name: Nicholas E
full_name: Propson, Nicholas E
last_name: Propson
- first_name: Yubin
full_name: Huang, Yubin
last_name: Huang
- first_name: Katherine
full_name: Poinsatte, Katherine
last_name: Poinsatte
- first_name: Zhaohuan
full_name: Zhang, Zhaohuan
last_name: Zhang
- first_name: Yuanlei
full_name: Yue, Yuanlei
last_name: Yue
- first_name: Dale B
full_name: Bosco, Dale B
last_name: Bosco
- first_name: Ying-mei
full_name: Lu, Ying-mei
last_name: Lu
- first_name: Shi-bing
full_name: Yang, Shi-bing
last_name: Yang
- first_name: Ralf H.
full_name: Adams, Ralf H.
last_name: Adams
- first_name: Volkhard
full_name: Lindner, Volkhard
last_name: Lindner
- first_name: Fen
full_name: Huang, Fen
last_name: Huang
- first_name: Long-Jun
full_name: Wu, Long-Jun
last_name: Wu
- first_name: Hui
full_name: Zheng, Hui
last_name: Zheng
- first_name: Feng
full_name: Han, Feng
last_name: Han
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Ann M.
full_name: Stowe, Ann M.
last_name: Stowe
- first_name: Bo
full_name: Peng, Bo
last_name: Peng
- first_name: Marta
full_name: Margeta, Marta
last_name: Margeta
- first_name: Xiaoqun
full_name: Wang, Xiaoqun
last_name: Wang
- first_name: Qiang
full_name: Liu, Qiang
last_name: Liu
- first_name: Jakob
full_name: Körbelin, Jakob
last_name: Körbelin
- first_name: Martin
full_name: Trepel, Martin
last_name: Trepel
- first_name: Hui
full_name: Lu, Hui
last_name: Lu
- first_name: Bo O.
full_name: Zhou, Bo O.
last_name: Zhou
- first_name: Hu
full_name: Zhao, Hu
last_name: Zhao
- first_name: Wenzhi
full_name: Su, Wenzhi
last_name: Su
- first_name: Robert M.
full_name: Bachoo, Robert M.
last_name: Bachoo
- first_name: Woo-ping
full_name: Ge, Woo-ping
last_name: Ge
citation:
ama: Gao X, Li J-L, Chen X, et al. Reduction of neuronal activity mediated by blood-vessel
regression in the brain. Nature Communications. 2025;16. doi:10.1038/s41467-025-60308-0
apa: Gao, X., Li, J.-L., Chen, X., Ci, B., Chen, F., Lu, N., … Ge, W. (2025). Reduction
of neuronal activity mediated by blood-vessel regression in the brain. Nature
Communications. Springer Nature. https://doi.org/10.1038/s41467-025-60308-0
chicago: Gao, Xiaofei, Jun-Liszt Li, Xingjun Chen, Bo Ci, Fei Chen, Nannan Lu, Bo
Shen, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel Regression
in the Brain.” Nature Communications. Springer Nature, 2025. https://doi.org/10.1038/s41467-025-60308-0.
ieee: X. Gao et al., “Reduction of neuronal activity mediated by blood-vessel
regression in the brain,” Nature Communications, vol. 16. Springer Nature,
2025.
ista: Gao X, Li J-L, Chen X, Ci B, Chen F, Lu N, Shen B, Zheng L, Jia J-M, Yi Y,
Zhang S, Shi Y-C, Shi K, Propson NE, Huang Y, Poinsatte K, Zhang Z, Yue Y, Bosco
DB, Lu Y, Yang S, Adams RH, Lindner V, Huang F, Wu L-J, Zheng H, Han F, Hippenmeyer
S, Stowe AM, Peng B, Margeta M, Wang X, Liu Q, Körbelin J, Trepel M, Lu H, Zhou
BO, Zhao H, Su W, Bachoo RM, Ge W. 2025. Reduction of neuronal activity mediated
by blood-vessel regression in the brain. Nature Communications. 16, 5840.
mla: Gao, Xiaofei, et al. “Reduction of Neuronal Activity Mediated by Blood-Vessel
Regression in the Brain.” Nature Communications, vol. 16, 5840, Springer
Nature, 2025, doi:10.1038/s41467-025-60308-0.
short: X. Gao, J.-L. Li, X. Chen, B. Ci, F. Chen, N. Lu, B. Shen, L. Zheng, J.-M.
Jia, Y. Yi, S. Zhang, Y.-C. Shi, K. Shi, N.E. Propson, Y. Huang, K. Poinsatte,
Z. Zhang, Y. Yue, D.B. Bosco, Y. Lu, S. Yang, R.H. Adams, V. Lindner, F. Huang,
L.-J. Wu, H. Zheng, F. Han, S. Hippenmeyer, A.M. Stowe, B. Peng, M. Margeta, X.
Wang, Q. Liu, J. Körbelin, M. Trepel, H. Lu, B.O. Zhou, H. Zhao, W. Su, R.M. Bachoo,
W. Ge, Nature Communications 16 (2025).
date_created: 2020-10-06T08:58:59Z
date_published: 2025-07-01T00:00:00Z
date_updated: 2025-09-04T07:08:37Z
day: '01'
ddc:
- '570'
department:
- _id: SiHi
doi: 10.1038/s41467-025-60308-0
ec_funded: 1
external_id:
isi:
- '001523450500035'
file:
- access_level: open_access
checksum: f59748cb67232cfb210035d9aef60836
content_type: application/pdf
creator: dernst
date_created: 2025-07-07T09:52:46Z
date_updated: 2025-07-07T09:52:46Z
file_id: '19971'
file_name: 2025_NatureComm_Gao.pdf
file_size: 17018106
relation: main_file
success: 1
file_date_updated: 2025-07-07T09:52:46Z
fulldoi: https://doi.org/10.1038/s41467-025-60308-0
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
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: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Reduction of neuronal activity mediated by blood-vessel regression in the brain
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: 16
year: '2025'
...
---
OA_place: repository
OA_type: green
_id: '19762'
abstract:
- lang: eng
text: The cerebral cortex must contain the appropriate numbers of neurons in each
layer to acquire its proper functional organization. Accordingly, neurogenesis
requires precise regulation along development. Cortical neurons are made either
directly by Radial Glia Cells (RGCs) that self- consume, or indirectly from RGCs
via Intermediate Progenitor Cells (IPCs) and largely preserving the RGC pool.
According to the standing model of cortical development, Direct Neurogenesis predominates
at early stages of development, and progressively shifts to Indirect Neurogenesis,
which predominates at late stages. However, neurogenesis at early stages should
be compatible with RGC amplification, and neurogenesis at late stages needs to
involve RGC consumption, which seems in conflict with the standing model. Here
we studied the modes of neurogenesis along cortical development using multiple
approaches, including birthdating, live imaging and MADM clone labeling. Contrary
to the established dogma, our data show that Indirect Neurogenesis clearly predominates
at early developmental stages, gradually shifting to Direct Neurogenesis at late
stages. These findings challenge the current model of cortical neurogenesis, and
prompt a re-evaluation of previous and ongoing work about the genetic and molecular
mechanisms regulating this process.
acknowledgement: "We thank A. Iñigo for assistance with imaging, and members of the
Borrell and Herrera labs for\r\ninsightful discussions and critical reading of the
manuscript. Funding to our lab members was\r\nprovided by the Spanish Research Agency
(AEI): FPI contract (BES-2016-077737) to L.dV.A., FPI SO contract (SEV-2017-0723-18-1)
to A.E., JdC-Incorporación contract (IJC2020-044653-I) to V.F., and JAE-Intro fellowship
(JAEICU23EX_0071) to I.C., as well as by La Caixa Foundation: La Caixa-Severo Ochoa
fellowship (E-03-2016-0557140) to S.A., INPhINIT-Retaining fellowship (LCF/BQ/DR21/11880012)
to E.F.O., INPhINIT-Incoming fellowship (LCF/BQ/DI22/11940006) to E.N., and Junior
Leader-Retaining grant to A.C. (LCF/BQ/PR23/11980051). Work was supported by grants
from FWF (SFB F78) to S.H.; AEI (PID2021-125618NB-I00) and European Research Council
(101118729) to V.B., who also acknowledges financial support from AEI through the
“Severo Ochoa” Programme for Centers of Excellence in R&D (CEX2021-001165-S)."
article_processing_charge: No
author:
- first_name: Adrián
full_name: Cárdenas, Adrián
last_name: Cárdenas
- first_name: Irem
full_name: Çelik, Irem
last_name: Çelik
- first_name: Alexandre
full_name: Espinós, Alexandre
last_name: Espinós
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Lara
full_name: López-González, Lara
last_name: López-González
- first_name: Lucia
full_name: del-Valle-Anton, Lucia
last_name: del-Valle-Anton
- first_name: Virginia
full_name: Fernández, Virginia
last_name: Fernández
- first_name: Salma
full_name: Amin, Salma
last_name: Amin
- first_name: Enrico
full_name: Negri, Enrico
last_name: Negri
- first_name: Eduardo Fernández
full_name: Ortuño, Eduardo Fernández
last_name: Ortuño
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: Víctor
full_name: Borrell, Víctor
last_name: Borrell
biorxivid: 1
citation:
ama: Cárdenas A, Çelik I, Espinós A, et al. Early indirect neurogenesis transitions
to late direct neurogenesis in mouse cerebral cortex development. bioRxiv.
doi:10.1101/2025.05.22.655488
apa: Cárdenas, A., Çelik, I., Espinós, A., Streicher, C., López-González, L., del-Valle-Anton,
L., … Borrell, V. (n.d.). Early indirect neurogenesis transitions to late direct
neurogenesis in mouse cerebral cortex development. bioRxiv. https://doi.org/10.1101/2025.05.22.655488
chicago: Cárdenas, Adrián, Irem Çelik, Alexandre Espinós, Carmen Streicher, Lara
López-González, Lucia del-Valle-Anton, Virginia Fernández, et al. “Early Indirect
Neurogenesis Transitions to Late Direct Neurogenesis in Mouse Cerebral Cortex
Development.” BioRxiv, n.d. https://doi.org/10.1101/2025.05.22.655488.
ieee: A. Cárdenas et al., “Early indirect neurogenesis transitions to late
direct neurogenesis in mouse cerebral cortex development,” bioRxiv. .
ista: Cárdenas A, Çelik I, Espinós A, Streicher C, López-González L, del-Valle-Anton
L, Fernández V, Amin S, Negri E, Ortuño EF, Hippenmeyer S, Borrell V. Early indirect
neurogenesis transitions to late direct neurogenesis in mouse cerebral cortex
development. bioRxiv, 10.1101/2025.05.22.655488.
mla: Cárdenas, Adrián, et al. “Early Indirect Neurogenesis Transitions to Late Direct
Neurogenesis in Mouse Cerebral Cortex Development.” BioRxiv, doi:10.1101/2025.05.22.655488.
short: A. Cárdenas, I. Çelik, A. Espinós, C. Streicher, L. López-González, L. del-Valle-Anton,
V. Fernández, S. Amin, E. Negri, E.F. Ortuño, S. Hippenmeyer, V. Borrell, BioRxiv
(n.d.).
date_created: 2025-05-29T10:45:55Z
date_published: 2025-05-23T00:00:00Z
date_updated: 2026-08-13T07:18:38Z
day: '23'
department:
- _id: SiHi
doi: 10.1101/2025.05.22.655488
external_id:
biorxivid:
- 10.1101/2025.05.22.655488
fulldoi: https://doi.org/10.1101/2025.05.22.655488
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2025.05.22.655488
month: '05'
oa: 1
oa_version: Preprint
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
publication: bioRxiv
publication_status: submitted
status: public
title: Early indirect neurogenesis transitions to late direct neurogenesis in mouse
cerebral cortex development
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: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
OA_place: repository
OA_type: green
_id: '19717'
abstract:
- lang: eng
text: Radial glial progenitors (RGPs) generate all projection neurons (PNs) in the
cerebral cortex through incompletely understood processes. Herein, we combine
Mosaic Analysis with Double Markers (MADM)-based clonal analysis at embryonic
days 12.5 and 13.5 with early postnatal callosal tracing to reveal a lineage progression
that challenges the inside-outside model of cortical development and the conventional
view of an invariable sequence of asymmetric neurogenic divisions. Our data demonstrate
that early multipotent RGPs generate all extra-telencephalic (ET) and intra-telencephalic
(IT) PNs across all layers through parallel sublineages and the random specification,
during the earliest neurogenic divisions, of fate-restricted daughter RGPs. While
the neuronal production of the parental multipotent RGPs consists of small ET-PN
or IT-PN outputs, fate-restricted RGPs produce larger translaminar outputs spanning
deep and upper layers of only IT-PNs, the predominant mammalian PN subtype. We
further show that the emergence of IT-PN fate-restricted RGPs also leads to quantitatively
and temporally stereotyped neurogenesis population-wise.
acknowledgement: "We thank M. Caouyette for the plasmid construction for Pou3f1 overexpression;
C. Varela747 Martínez for help with the code for graphical analysis; all members
from the Nieto’s lab for\r\ncomment on the manuscript, specially to F. Martín for
the insightful discussions;J.C. Oliveros\r\nand J.A. García from the computational
service of the CNB for help with the analysis of\r\nRNAseq dataset, C.O. Sorzano
for the help with statistical analysis, and the service of\r\nAdvance Optical Microscopy
of the CNB for their technical advice.\r\nI.V.M holds a fellowship funded by MCICIU
(PRE-2018-083376), the work was funded by\r\nPID2020-112831GB-I00 funded by MCIN/AEI
/10.13039/501100011033.\r\n"
article_processing_charge: No
author:
- first_name: I
full_name: Varela-Martínez, I
last_name: Varela-Martínez
- first_name: Ana
full_name: Villalba Requena, Ana
id: 68cb85a0-39f7-11eb-9559-9aaab4f6a247
last_name: Villalba Requena
orcid: 0000-0002-5615-5277
- first_name: J.
full_name: Garcia-Marqués, J.
last_name: Garcia-Marqués
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
- first_name: M.
full_name: Nieto, M.
last_name: Nieto
citation:
ama: Varela-Martínez I, Villalba Requena A, Garcia-Marqués J, Hippenmeyer S, Nieto
M. Early emergence of projection-subtype fate-restricted radial glial progenitors
orchestrates neocortical neurogenesis. bioRxiv. doi:10.1101/2025.05.07.652665
apa: Varela-Martínez, I., Villalba Requena, A., Garcia-Marqués, J., Hippenmeyer,
S., & Nieto, M. (n.d.). Early emergence of projection-subtype fate-restricted
radial glial progenitors orchestrates neocortical neurogenesis. bioRxiv.
https://doi.org/10.1101/2025.05.07.652665
chicago: Varela-Martínez, I, Ana Villalba Requena, J. Garcia-Marqués, Simon Hippenmeyer,
and M. Nieto. “Early Emergence of Projection-Subtype Fate-Restricted Radial Glial
Progenitors Orchestrates Neocortical Neurogenesis.” BioRxiv, n.d. https://doi.org/10.1101/2025.05.07.652665.
ieee: I. Varela-Martínez, A. Villalba Requena, J. Garcia-Marqués, S. Hippenmeyer,
and M. Nieto, “Early emergence of projection-subtype fate-restricted radial glial
progenitors orchestrates neocortical neurogenesis,” bioRxiv. .
ista: Varela-Martínez I, Villalba Requena A, Garcia-Marqués J, Hippenmeyer S, Nieto
M. Early emergence of projection-subtype fate-restricted radial glial progenitors
orchestrates neocortical neurogenesis. bioRxiv, 10.1101/2025.05.07.652665.
mla: Varela-Martínez, I., et al. “Early Emergence of Projection-Subtype Fate-Restricted
Radial Glial Progenitors Orchestrates Neocortical Neurogenesis.” BioRxiv,
doi:10.1101/2025.05.07.652665.
short: I. Varela-Martínez, A. Villalba Requena, J. Garcia-Marqués, S. Hippenmeyer,
M. Nieto, BioRxiv (n.d.).
date_created: 2025-05-20T10:19:29Z
date_published: 2025-05-07T00:00:00Z
date_updated: 2026-08-13T07:16:48Z
day: '07'
department:
- _id: SiHi
doi: 10.1101/2025.05.07.652665
fulldoi: https://doi.org/10.1101/2025.05.07.652665
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2025.05.07.652665
month: '05'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: submitted
status: public
title: Early emergence of projection-subtype fate-restricted radial glial progenitors
orchestrates neocortical neurogenesis
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
OA_place: publisher
_id: '20212'
abstract:
- lang: eng
text: "Cortical development has been studied for many decades and with each passing
year, we learn \r\nmore about the processes that govern the tightly regulated
developmental program. Up until \r\nrecently, the field has struggled to gain
reliable access to progenitors at the single-cell level, \r\nlimiting the resolution
at which we can study cortical development in vivo. Therefore, much of \r\nthe
data we have on mammalian cortical development is at the cell population level.
The \r\nsubsequent pages of this thesis describe novel elements of cortical development
in mice; \r\nacquired using a candidate gene approach in conjunction with Mosaic
Analysis with Double \r\nMarkers (MADM) to achieve single cell resolution. In
this thesis, I briefly provide an overview \r\nof the state of the field, describe
the methodology used to quantify morphological \r\ncharacteristics of neurons
and glia, and delve into the role of Phosphatase and tensin \r\nhomologue on chromosome
ten (Pten) in neurogenesis and gliogenesis in the developing mouse \r\ncortex.
By using MADM to generate genetic mosaics, in which only a small fraction of cells
\r\nare mutated, to study population-level changes, we can bypass the early postnatal
lethality \r\nreported in Pten conditional knockouts (cKOs) using Emx1-Cre. We
used Emx1-CreERT2 to \r\ninduce clonal deletion of Pten, and quantify RGP neurogenic
output at the single progenitor \r\nlevel. Pten-mutant neuron populations within
the mosaics were significantly expanded. In the \r\nlatter parts of this thesis,
we describe how Pten deletion leads to an increase in the abundance \r\nof astrocytes.
We availed ourselves of the flexibility offered by the MADM system to generate
\r\nPten mosaics within a series of distinct knockout tissues to test for the
interactions between \r\nPten and a battery of genes involved in distinct pro-gliogenic
signaling pathways. Our survey \r\nof Pten’s interactions with genes in key signaling
pathways reveals that ERK1/2 are the critical \r\neffectors downstream of EGFR
signaling essential for gliogenesis. Altogether, our results \r\ndemonstrate that
Pten plays critical and distinct roles throughout cortical RGP lineage \r\nprogression. "
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: "I would also like to\r\nthank the Austrian Academy of Sciences for
awarding me a 2-year DOC fellowship\r\n(DOC26253)."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Osvaldo
full_name: Miranda, Osvaldo
id: 862A3C56-A8BF-11E9-B4FA-D9E3E5697425
last_name: Miranda
orcid: 0000-0001-6618-6889
citation:
ama: Miranda O. Unraveling the role of Pten in cortical stem cell lineage progression
using MADM. 2025. doi:10.15479/AT-ISTA-20212
apa: Miranda, O. (2025). Unraveling the role of Pten in cortical stem cell lineage
progression using MADM. Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-20212
chicago: Miranda, Osvaldo. “Unraveling the Role of Pten in Cortical Stem Cell Lineage
Progression Using MADM.” Institute of Science and Technology Austria, 2025. https://doi.org/10.15479/AT-ISTA-20212.
ieee: O. Miranda, “Unraveling the role of Pten in cortical stem cell lineage progression
using MADM,” Institute of Science and Technology Austria, 2025.
ista: Miranda O. 2025. Unraveling the role of Pten in cortical stem cell lineage
progression using MADM. Institute of Science and Technology Austria.
mla: Miranda, Osvaldo. Unraveling the Role of Pten in Cortical Stem Cell Lineage
Progression Using MADM. Institute of Science and Technology Austria, 2025,
doi:10.15479/AT-ISTA-20212.
short: O. Miranda, Unraveling the Role of Pten in Cortical Stem Cell Lineage Progression
Using MADM, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-08-22T14:07:00Z
date_published: 2025-08-22T00:00:00Z
date_updated: 2026-10-02T12:16:56Z
day: '22'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: SiHi
doi: 10.15479/AT-ISTA-20212
doi_confirm: '1'
file:
- access_level: closed
checksum: 3331f76bbef74ff4908e2d2c9262045c
content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
creator: omiranda
date_created: 2025-08-26T09:03:50Z
date_updated: 2026-08-26T22:30:02Z
embargo_to: open_access
file_id: '20230'
file_name: 2025_MirandaRomero_OsvaldoAntonio_Thesis.docx
file_size: 32887334
relation: source_file
- access_level: open_access
checksum: 02509d50cff8e35c5bcbf71e8d658176
content_type: application/pdf
creator: omiranda
date_created: 2025-08-26T09:05:55Z
date_updated: 2026-08-26T22:30:02Z
embargo: 2026-08-26
file_id: '20231'
file_name: 2025_MirandaRomero_OsvaldoAntonio_Thesis.pdf
file_size: 28636240
relation: main_file
file_date_updated: 2026-08-26T22:30:02Z
fulldoi: https://doi.org/10.15479/AT-ISTA-20212
has_accepted_license: '1'
keyword:
- Pten
- mtor
- cortical development
- MADM
- Mapk
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: '119'
project:
- _id: 34c9fbcb-11ca-11ed-8bc3-98fa5658610d
grant_number: '26253'
name: Molecular Mechanisms Regulating Cortical Neural Stem Cell Lineage Progression
and Astrocyte Development
publication_identifier:
isbn:
- 978-3-99078-063-3
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '17425'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
title: Unraveling the role of Pten in cortical stem cell lineage progression using
MADM
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
_id: '12875'
abstract:
- lang: eng
text: The superior colliculus (SC) in the mammalian midbrain is essential for multisensory
integration and is composed of a rich diversity of excitatory and inhibitory neurons
and glia. However, the developmental principles directing the generation of SC
cell-type diversity are not understood. Here, we pursued systematic cell lineage
tracing in silico and in vivo, preserving full spatial information, using genetic
mosaic analysis with double markers (MADM)-based clonal analysis with single-cell
sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed
that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual
resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron
types, even at the stage of terminal division. While individual clonal units show
no pre-defined cellular composition, the establishment of appropriate relative
proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively,
our findings provide an inaugural framework at the single-RGP/-cell level of the
mammalian SC ontogeny.
acknowledged_ssus:
- _id: Bio
- _id: M-Shop
- _id: LifeSc
- _id: PreCl
acknowledgement: "We thank Liqun Luo for his continued support, for providing essential
resources for generating Fzd10-CreER mice which were generated in his laboratory,
and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic
mouse line for this study; A. Heger for mouse colony management; R. Beattie and
T. Asenov for designing and producing components of acute slice recovery chamber
for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial
experiments, technical support and/or assistance. This study was supported by the
Scientific Service Units (SSU) of IST Austria through resources provided by the
Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine
Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission
(IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds;
the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation)
to S.H. "
article_processing_charge: Yes (via OA deal)
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: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
orcid: 0000-0002-7462-0048
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
orcid: 0000-0002-3509-1948
- first_name: Thomas
full_name: Krausgruber, Thomas
last_name: Krausgruber
- first_name: Carmen
full_name: Streicher, Carmen
id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
last_name: Streicher
- first_name: Martin
full_name: Schrammel, Martin
id: f13e7cae-e8bd-11ed-841a-96dedf69f46d
last_name: Schrammel
- first_name: Natalie Y
full_name: Özgen, Natalie Y
id: e68ece33-f6e0-11ea-865d-ae1031dcc090
last_name: Özgen
- first_name: Alexis
full_name: Ivec, Alexis
id: 1d144691-e8be-11ed-9b33-bdd3077fad4c
last_name: Ivec
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Simon
full_name: Hippenmeyer, Simon
id: 37B36620-F248-11E8-B48F-1D18A9856A87
last_name: Hippenmeyer
orcid: 0000-0003-2279-1061
citation:
ama: Cheung GT, Pauler F, Koppensteiner P, et al. Multipotent progenitors instruct
ontogeny of the superior colliculus. Neuron. 2024;112(2):230-246.e11. doi:10.1016/j.neuron.2023.11.009
apa: Cheung, G. T., Pauler, F., Koppensteiner, P., Krausgruber, T., Streicher, C.,
Schrammel, M., … Hippenmeyer, S. (2024). Multipotent progenitors instruct ontogeny
of the superior colliculus. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.11.009
chicago: Cheung, Giselle T, Florian Pauler, Peter Koppensteiner, Thomas Krausgruber,
Carmen Streicher, Martin Schrammel, Natalie Y Özgen, et al. “Multipotent Progenitors
Instruct Ontogeny of the Superior Colliculus.” Neuron. Elsevier, 2024.
https://doi.org/10.1016/j.neuron.2023.11.009.
ieee: G. T. Cheung et al., “Multipotent progenitors instruct ontogeny of
the superior colliculus,” Neuron, vol. 112, no. 2. Elsevier, p. 230–246.e11,
2024.
ista: Cheung GT, Pauler F, Koppensteiner P, Krausgruber T, Streicher C, Schrammel
M, Özgen NY, Ivec A, Bock C, Shigemoto R, Hippenmeyer S. 2024. Multipotent progenitors
instruct ontogeny of the superior colliculus. Neuron. 112(2), 230–246.e11.
mla: Cheung, Giselle T., et al. “Multipotent Progenitors Instruct Ontogeny of the
Superior Colliculus.” Neuron, vol. 112, no. 2, Elsevier, 2024, p. 230–246.e11,
doi:10.1016/j.neuron.2023.11.009.
short: G.T. Cheung, F. Pauler, P. Koppensteiner, T. Krausgruber, C. Streicher, M.
Schrammel, N.Y. Özgen, A. Ivec, C. Bock, R. Shigemoto, S. Hippenmeyer, Neuron
112 (2024) 230–246.e11.
corr_author: '1'
date_created: 2023-04-27T09:41:48Z
date_published: 2024-01-17T00:00:00Z
date_updated: 2025-12-30T10:54:12Z
day: '17'
ddc:
- '570'
department:
- _id: SiHi
- _id: RySh
doi: 10.1016/j.neuron.2023.11.009
external_id:
isi:
- '001163937900001'
pmid:
- '38096816'
file:
- access_level: open_access
checksum: 32b3788f7085cf44a84108d8faaff3ce
content_type: application/pdf
creator: dernst
date_created: 2024-02-06T13:56:15Z
date_updated: 2024-02-06T13:56:15Z
file_id: '14944'
file_name: 2024_Neuron_Cheung.pdf
file_size: 5942467
relation: main_file
success: 1
file_date_updated: 2024-02-06T13:56:15Z
fulldoi: https://doi.org/10.1016/j.neuron.2023.11.009
has_accepted_license: '1'
intvolume: ' 112'
isi: 1
issue: '2'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 230-246.e11
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
grant_number: F7805
name: Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular
Mechanisms of Neural Stem Cell Lineage Progression
publication: Neuron
publication_identifier:
issn:
- 0896-6273
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/the-pedigree-of-brain-cells/
scopus_import: '1'
status: public
title: Multipotent progenitors instruct ontogeny of the superior colliculus
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: 112
year: '2024'
...