---
OA_place: repository
OA_type: green
_id: '21920'
abstract:
- lang: eng
text: 'Vertebrates display remarkable diversity of sensorimotor behaviors, each
adapted to distinct ecological and survival demands. This diversity raises fundamental
questions about the evolutionary origin of motor control: do conserved spinal
circuits underlie these behaviors, and how have they diverged across species.
Recent studies detail spinal cell-type architecture in mammals but comparable,
high-resolution atlases of the non-mammalian spinal cord are lacking. Here, we
compare spinal cord cell types between fish, frogs, mice and humans, spanning
∼450 million years of evolution. Across species, we define highly conserved programs
of cell type specification that segregate spinal neurons into nearly identical
cardinal classes during development. This contrasts with adult stages, when spinal
cell-type composition selectively diverges for excitatory neuron subpopulations.
Using spatial transcriptomics, we localize this species divergence to the superficial,
dorsal spinal cord, where variant neuropeptide expression defines mammalian-specific
cell types. The most dorsal spinal cord thus emerges as a recently evolved hub
for sensory integration in mammals, a neospinal cord analogous to the neocortex.'
acknowledgement: "We would like to thank the members of the Sweeney Lab for discussion
and support; Andrey\r\nBydanov for technical assistance with single-cell sequencing
processing; and Jay Bikoff,\r\nNikos Konstantinides, Maria Tosches, and Graziana
Gatto for comments on the manuscript. \r\nThis research was supported by: Horizon
Europe ERC Starting Grant 101041551 (L.B.S,\r\nY.I., S.P.); Special Research Program
(SFB) of the Austrian Science Fund (FWF) F7814-B\r\n(L.B.S., S.P., E.M.T); Austrian
Science Fund (FWF) 10.55776/COE16 (L.B.S., Y.I., E.M.T.);\r\nAustrian Academy of
Sciences DOC Fellowship 27229 (S.P.); ERC Advanced Grant 742046\r\n(E.M.T.); NIH
award R24 OD031956 (L.P.); and in part by the Intramural Research\r\nProgram of
the National Institutes of Health (NIH) through 1ZIA NS003153 to A.J.L.\r\nThe contributions
of the NIH author are considered Works of the United States\r\nGovernment. The findings
and conclusions presented in this paper are those of\r\nthe authors and do not necessarily
reflect the views of the NIH or the U.S. Department\r\nof Health and Human Services. "
article_processing_charge: No
author:
- first_name: Yuri
full_name: Ignatyev, Yuri
last_name: Ignatyev
- first_name: Stavros
full_name: Papadopoulos, Stavros
id: 40606b92-f128-11eb-9611-bf66a98cfa5c
last_name: Papadopoulos
- first_name: Mateja
full_name: Soretić, Mateja
last_name: Soretić
- first_name: Jake
full_name: Yeung, Jake
id: 123012b2-db30-11eb-b4d8-a35840c0551b
last_name: Yeung
orcid: 0000-0003-1732-1559
- first_name: Tzi-Yang
full_name: Lin, Tzi-Yang
last_name: Lin
- first_name: Elly M
full_name: Tanaka, Elly M
last_name: Tanaka
- first_name: Leonid
full_name: Peshkin, Leonid
last_name: Peshkin
- first_name: Ariel J
full_name: Levine, Ariel J
last_name: Levine
- first_name: Mariano I
full_name: Gabitto, Mariano I
last_name: Gabitto
- 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: Ignatyev Y, Papadopoulos S, Soretić M, et al. Innovations in spinal cord cell
type heterogeneity across vertebrate evolution. bioRxiv. doi:10.1101/2025.10.09.680955
apa: Ignatyev, Y., Papadopoulos, S., Soretić, M., Yeung, J., Lin, T.-Y., Tanaka,
E. M., … Sweeney, L. B. (n.d.). Innovations in spinal cord cell type heterogeneity
across vertebrate evolution. bioRxiv. https://doi.org/10.1101/2025.10.09.680955
chicago: Ignatyev, Yuri, Stavros Papadopoulos, Mateja Soretić, Jake Yeung, Tzi-Yang
Lin, Elly M Tanaka, Leonid Peshkin, Ariel J Levine, Mariano I Gabitto, and Lora
B. Sweeney. “Innovations in Spinal Cord Cell Type Heterogeneity across Vertebrate
Evolution.” BioRxiv, n.d. https://doi.org/10.1101/2025.10.09.680955.
ieee: Y. Ignatyev et al., “Innovations in spinal cord cell type heterogeneity
across vertebrate evolution,” bioRxiv. .
ista: Ignatyev Y, Papadopoulos S, Soretić M, Yeung J, Lin T-Y, Tanaka EM, Peshkin
L, Levine AJ, Gabitto MI, Sweeney LB. Innovations in spinal cord cell type heterogeneity
across vertebrate evolution. bioRxiv, 10.1101/2025.10.09.680955.
mla: Ignatyev, Yuri, et al. “Innovations in Spinal Cord Cell Type Heterogeneity
across Vertebrate Evolution.” BioRxiv, doi:10.1101/2025.10.09.680955.
short: Y. Ignatyev, S. Papadopoulos, M. Soretić, J. Yeung, T.-Y. Lin, E.M. Tanaka,
L. Peshkin, A.J. Levine, M.I. Gabitto, L.B. Sweeney, BioRxiv (n.d.).
corr_author: '1'
date_created: 2026-05-27T06:54:04Z
date_published: 2025-10-11T00:00:00Z
date_updated: 2026-05-27T07:25:41Z
day: '11'
department:
- _id: LoSw
- _id: ScienComp
doi: 10.1101/2025.10.09.680955
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2025.10.09.680955
month: '10'
oa: 1
oa_version: Preprint
project:
- _id: ebb66355-77a9-11ec-83b8-b8ac210a4dae
grant_number: '101041551'
name: Development and Evolution of Tetrapod Motor Circuits
- _id: 907b765e-16d5-11f0-9cad-fef108a945b1
grant_number: '27229'
name: 'A Tale of Two Circuits: Rostrocaudal spinal cord patterning during the swim-to-limb
transition of Xenopus metamorphosis'
publication: bioRxiv
publication_status: submitted
status: public
title: Innovations in spinal cord cell type heterogeneity across vertebrate evolution
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: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2025'
...
---
_id: '12106'
abstract:
- lang: eng
text: Regulation of chromatin states involves the dynamic interplay between different
histone modifications to control gene expression. Recent advances have enabled
mapping of histone marks in single cells, but most methods are constrained to
profile only one histone mark per cell. Here, we present an integrated experimental
and computational framework, scChIX-seq (single-cell chromatin immunocleavage
and unmixing sequencing), to map several histone marks in single cells. scChIX-seq
multiplexes two histone marks together in single cells, then computationally deconvolves
the signal using training data from respective histone mark profiles. This framework
learns the cell-type-specific correlation structure between histone marks, and
therefore does not require a priori assumptions of their genomic distributions.
Using scChIX-seq, we demonstrate multimodal analysis of histone marks in single
cells across a range of mark combinations. Modeling dynamics of in vitro macrophage
differentiation enables integrated analysis of chromatin velocity. Overall, scChIX-seq
unlocks systematic interrogation of the interplay between histone modifications
in single cells.
acknowledgement: We thank M. van Loenhout for experimental advice on purifying cell
types from the bone marrow, R. van der Linden for expertise with FACS and M. Blotenburg
for help with cell typing the mouse organogenesis dataset. We thank M. Saraswat
and O. Stegle for discussions on multinomial distributions. This work was supported
by a European Research Council Advanced grant (ERC-AdG 742225-IntScOmics); Nederlandse
Organisatie voor Wetenschappelijk Onderzoek (NWO) TOP grant (NWO CW 714.016.001)
and NWO grant (OCENW.GROOT.2019.017); the Swiss National Science Foundation Early
Postdoc Mobility (P2ELP3-184488 to P.Z. and P2BSP3-174991 to J.Y.); Marie Sklodowska-Curie
Actions Postdoc (798573 to P.Z.) and the Human Frontier for Science Program Long-Term
Fellowships (LT000209-2018-L to P.Z. and LT000097-2019-L to J.Y.). This work is
part of the Oncode Institute which is financed partly by the Dutch Cancer Society.
article_processing_charge: No
article_type: original
author:
- first_name: Jake
full_name: Yeung, Jake
id: 123012b2-db30-11eb-b4d8-a35840c0551b
last_name: Yeung
orcid: 0000-0003-1732-1559
- first_name: Maria
full_name: Florescu, Maria
last_name: Florescu
- first_name: Peter
full_name: Zeller, Peter
last_name: Zeller
- first_name: Buys Anton
full_name: De Barbanson, Buys Anton
last_name: De Barbanson
- first_name: Max D.
full_name: Wellenstein, Max D.
last_name: Wellenstein
- first_name: Alexander
full_name: Van Oudenaarden, Alexander
last_name: Van Oudenaarden
citation:
ama: Yeung J, Florescu M, Zeller P, De Barbanson BA, Wellenstein MD, Van Oudenaarden
A. scChIX-seq infers dynamic relationships between histone modifications in single
cells. Nature Biotechnology. 2023;41:813–823. doi:10.1038/s41587-022-01560-3
apa: Yeung, J., Florescu, M., Zeller, P., De Barbanson, B. A., Wellenstein, M. D.,
& Van Oudenaarden, A. (2023). scChIX-seq infers dynamic relationships between
histone modifications in single cells. Nature Biotechnology. Springer Nature.
https://doi.org/10.1038/s41587-022-01560-3
chicago: Yeung, Jake, Maria Florescu, Peter Zeller, Buys Anton De Barbanson, Max
D. Wellenstein, and Alexander Van Oudenaarden. “ScChIX-Seq Infers Dynamic Relationships
between Histone Modifications in Single Cells.” Nature Biotechnology. Springer
Nature, 2023. https://doi.org/10.1038/s41587-022-01560-3.
ieee: J. Yeung, M. Florescu, P. Zeller, B. A. De Barbanson, M. D. Wellenstein, and
A. Van Oudenaarden, “scChIX-seq infers dynamic relationships between histone modifications
in single cells,” Nature Biotechnology, vol. 41. Springer Nature, pp. 813–823,
2023.
ista: Yeung J, Florescu M, Zeller P, De Barbanson BA, Wellenstein MD, Van Oudenaarden
A. 2023. scChIX-seq infers dynamic relationships between histone modifications
in single cells. Nature Biotechnology. 41, 813–823.
mla: Yeung, Jake, et al. “ScChIX-Seq Infers Dynamic Relationships between Histone
Modifications in Single Cells.” Nature Biotechnology, vol. 41, Springer
Nature, 2023, pp. 813–823, doi:10.1038/s41587-022-01560-3.
short: J. Yeung, M. Florescu, P. Zeller, B.A. De Barbanson, M.D. Wellenstein, A.
Van Oudenaarden, Nature Biotechnology 41 (2023) 813–823.
corr_author: '1'
date_created: 2023-01-08T23:00:53Z
date_published: 2023-06-01T00:00:00Z
date_updated: 2025-04-23T08:45:24Z
day: '01'
ddc:
- '570'
department:
- _id: ScienComp
doi: 10.1038/s41587-022-01560-3
external_id:
isi:
- '000909067600003'
pmid:
- '36593403'
file:
- access_level: open_access
checksum: 668447a1c8d360b68f8aaf9e08ed644f
content_type: application/pdf
creator: dernst
date_created: 2023-08-16T11:30:45Z
date_updated: 2023-08-16T11:30:45Z
file_id: '14066'
file_name: 2023_NatureBioTech_Yeung.pdf
file_size: 12040976
relation: main_file
success: 1
file_date_updated: 2023-08-16T11:30:45Z
has_accepted_license: '1'
intvolume: ' 41'
isi: 1
language:
- iso: eng
month: '06'
oa: 1
oa_version: Published Version
page: 813–823
pmid: 1
publication: Nature Biotechnology
publication_identifier:
eissn:
- 1546-1696
issn:
- 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: scChIX-seq infers dynamic relationships between histone modifications in single
cells
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: 41
year: '2023'
...
---
_id: '12158'
abstract:
- lang: eng
text: 'Post-translational histone modifications modulate chromatin activity to affect
gene expression. How chromatin states underlie lineage choice in single cells
is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage
(sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3)
histone modifications in the mouse bone marrow. During differentiation, hematopoietic
stem and progenitor cells (HSPCs) acquire active chromatin states mediated by
cell-type-specifying transcription factors, which are unique for each lineage.
By contrast, most alterations in repressive marks during differentiation occur
independent of the final cell type. Chromatin trajectory analysis shows that lineage
choice at the chromatin level occurs at the progenitor stage. Joint profiling
of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage
have distinct active chromatin but share similar myeloid-specific heterochromatin
states. This implies a hierarchical regulation of chromatin during hematopoiesis:
heterochromatin dynamics distinguish differentiation trajectories and lineages,
while euchromatin dynamics reflect cell types within lineages.'
acknowledgement: We thank A. Giladi for sharing mRNA abundance tables of cell types
together with J. van den Berg for critical reading of the manuscript. We thank M.
Bartosovic for sharing method comparison data. pK19pA-MN was a gift from Ulrich
Laemmli (Addgene plasmid 86973, http://n2t.net/addgene:86973; RRID:Addgene_86973).
Figure 8 is adopted from Hematopoiesis (human) diagram by A. Rad and M. Häggström
under CC-BY-SA 3.0 license. This work was supported by European Research Council
Advanced under grant ERC-AdG 742225-IntScOmics and Nederlandse Organisatie voor
Wetenschappelijk Onderzoek (NWO) TOP award NWO-CW 714.016.001. The SNF (P2BSP3-174991),
HFSP (LT000209/2018-L) and Marie Skłodowska-Curie Actions (798573) supported P.Z.
The SNF (P2ELP3_184488) and HFSP (LT000097/2019-L) supported J.Y. and the EMBO LTF
(ALTF 1197–2019) supported V.B. This work is part of the Oncode Institute, which
is partly financed by the Dutch Cancer Society. The funders had no role in study
design, data collection and analysis, decision to publish or preparation of the
manuscript.
article_processing_charge: No
article_type: review
author:
- first_name: Peter
full_name: Zeller, Peter
last_name: Zeller
- first_name: Jake
full_name: Yeung, Jake
id: 123012b2-db30-11eb-b4d8-a35840c0551b
last_name: Yeung
orcid: 0000-0003-1732-1559
- first_name: Helena
full_name: Viñas Gaza, Helena
last_name: Viñas Gaza
- first_name: Buys Anton
full_name: de Barbanson, Buys Anton
last_name: de Barbanson
- first_name: Vivek
full_name: Bhardwaj, Vivek
last_name: Bhardwaj
- first_name: Maria
full_name: Florescu, Maria
last_name: Florescu
- first_name: Reinier
full_name: van der Linden, Reinier
last_name: van der Linden
- first_name: Alexander
full_name: van Oudenaarden, Alexander
last_name: van Oudenaarden
citation:
ama: Zeller P, Yeung J, Viñas Gaza H, et al. Single-cell sortChIC identifies hierarchical
chromatin dynamics during hematopoiesis. Nature Genetics. 2023;55:333-345.
doi:10.1038/s41588-022-01260-3
apa: Zeller, P., Yeung, J., Viñas Gaza, H., de Barbanson, B. A., Bhardwaj, V., Florescu,
M., … van Oudenaarden, A. (2023). Single-cell sortChIC identifies hierarchical
chromatin dynamics during hematopoiesis. Nature Genetics. Springer Nature.
https://doi.org/10.1038/s41588-022-01260-3
chicago: Zeller, Peter, Jake Yeung, Helena Viñas Gaza, Buys Anton de Barbanson,
Vivek Bhardwaj, Maria Florescu, Reinier van der Linden, and Alexander van Oudenaarden.
“Single-Cell SortChIC Identifies Hierarchical Chromatin Dynamics during Hematopoiesis.”
Nature Genetics. Springer Nature, 2023. https://doi.org/10.1038/s41588-022-01260-3.
ieee: P. Zeller et al., “Single-cell sortChIC identifies hierarchical chromatin
dynamics during hematopoiesis,” Nature Genetics, vol. 55. Springer Nature,
pp. 333–345, 2023.
ista: Zeller P, Yeung J, Viñas Gaza H, de Barbanson BA, Bhardwaj V, Florescu M,
van der Linden R, van Oudenaarden A. 2023. Single-cell sortChIC identifies hierarchical
chromatin dynamics during hematopoiesis. Nature Genetics. 55, 333–345.
mla: Zeller, Peter, et al. “Single-Cell SortChIC Identifies Hierarchical Chromatin
Dynamics during Hematopoiesis.” Nature Genetics, vol. 55, Springer Nature,
2023, pp. 333–45, doi:10.1038/s41588-022-01260-3.
short: P. Zeller, J. Yeung, H. Viñas Gaza, B.A. de Barbanson, V. Bhardwaj, M. Florescu,
R. van der Linden, A. van Oudenaarden, Nature Genetics 55 (2023) 333–345.
date_created: 2023-01-12T12:09:09Z
date_published: 2023-02-01T00:00:00Z
date_updated: 2025-04-23T08:45:00Z
day: '01'
ddc:
- '570'
- '000'
department:
- _id: ScienComp
doi: 10.1038/s41588-022-01260-3
external_id:
pmid:
- '36539617'
file:
- access_level: open_access
checksum: 6fdb8e34fbeea63edd0f2c6c2cc5823e
content_type: application/pdf
creator: dernst
date_created: 2023-02-27T07:46:45Z
date_updated: 2023-02-27T07:46:45Z
file_id: '12688'
file_name: 2023_NatureGenetics_Zeller.pdf
file_size: 21484855
relation: main_file
success: 1
file_date_updated: 2023-02-27T07:46:45Z
has_accepted_license: '1'
intvolume: ' 55'
keyword:
- Genetics
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 333-345
pmid: 1
publication: Nature Genetics
publication_identifier:
eissn:
- 1546-1718
issn:
- 1061-4036
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis
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: 55
year: '2023'
...