[{"_id":"21920","type":"preprint","article_processing_charge":"No","oa_version":"Preprint","day":"11","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. ","department":[{"_id":"LoSw"},{"_id":"ScienComp"}],"status":"public","citation":{"mla":"Ignatyev, Yuri, et al. “Innovations in Spinal Cord Cell Type Heterogeneity across Vertebrate Evolution.” <i>BioRxiv</i>, doi:<a href=\"https://doi.org/10.1101/2025.10.09.680955\">10.1101/2025.10.09.680955</a>.","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.).","ieee":"Y. Ignatyev <i>et al.</i>, “Innovations in spinal cord cell type heterogeneity across vertebrate evolution,” <i>bioRxiv</i>. .","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, <a href=\"https://doi.org/10.1101/2025.10.09.680955\">10.1101/2025.10.09.680955</a>.","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.” <i>BioRxiv</i>, n.d. <a href=\"https://doi.org/10.1101/2025.10.09.680955\">https://doi.org/10.1101/2025.10.09.680955</a>.","ama":"Ignatyev Y, Papadopoulos S, Soretić M, et al. Innovations in spinal cord cell type heterogeneity across vertebrate evolution. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2025.10.09.680955\">10.1101/2025.10.09.680955</a>","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. <i>bioRxiv</i>. <a href=\"https://doi.org/10.1101/2025.10.09.680955\">https://doi.org/10.1101/2025.10.09.680955</a>"},"OA_place":"repository","doi":"10.1101/2025.10.09.680955","corr_author":"1","OA_type":"green","date_published":"2025-10-11T00:00:00Z","publication":"bioRxiv","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","year":"2025","publication_status":"submitted","oa":1,"abstract":[{"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.</jats:p>","lang":"eng"}],"date_updated":"2026-05-27T07:25:41Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2025.10.09.680955"}],"date_created":"2026-05-27T06:54:04Z","title":"Innovations in spinal cord cell type heterogeneity across vertebrate evolution","author":[{"first_name":"Yuri","last_name":"Ignatyev","full_name":"Ignatyev, Yuri"},{"full_name":"Papadopoulos, Stavros","id":"40606b92-f128-11eb-9611-bf66a98cfa5c","first_name":"Stavros","last_name":"Papadopoulos"},{"last_name":"Soretić","first_name":"Mateja","full_name":"Soretić, Mateja"},{"full_name":"Yeung, Jake","id":"123012b2-db30-11eb-b4d8-a35840c0551b","last_name":"Yeung","first_name":"Jake","orcid":"0000-0003-1732-1559"},{"full_name":"Lin, Tzi-Yang","last_name":"Lin","first_name":"Tzi-Yang"},{"first_name":"Elly M","last_name":"Tanaka","full_name":"Tanaka, Elly M"},{"first_name":"Leonid","last_name":"Peshkin","full_name":"Peshkin, Leonid"},{"last_name":"Levine","first_name":"Ariel J","full_name":"Levine, Ariel J"},{"first_name":"Mariano I","last_name":"Gabitto","full_name":"Gabitto, Mariano I"},{"id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","full_name":"Sweeney, Lora Beatrice Jaeger","orcid":"0000-0001-9242-5601","first_name":"Lora Beatrice Jaeger","last_name":"Sweeney"}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","project":[{"_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae","grant_number":"101041551","name":"Development and Evolution of Tetrapod Motor Circuits"},{"_id":"907b765e-16d5-11f0-9cad-fef108a945b1","name":"A Tale of Two Circuits: Rostrocaudal spinal cord patterning during the swim-to-limb transition of Xenopus metamorphosis","grant_number":"27229"}],"month":"10"},{"date_published":"2023-06-01T00:00:00Z","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"publication_status":"published","file_date_updated":"2023-08-16T11:30:45Z","publication":"Nature Biotechnology","date_updated":"2025-04-23T08:45:24Z","abstract":[{"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.","lang":"eng"}],"date_created":"2023-01-08T23:00:53Z","external_id":{"isi":["000909067600003"],"pmid":["36593403"]},"author":[{"id":"123012b2-db30-11eb-b4d8-a35840c0551b","full_name":"Yeung, Jake","first_name":"Jake","last_name":"Yeung","orcid":"0000-0003-1732-1559"},{"full_name":"Florescu, Maria","first_name":"Maria","last_name":"Florescu"},{"last_name":"Zeller","first_name":"Peter","full_name":"Zeller, Peter"},{"full_name":"De Barbanson, Buys Anton","last_name":"De Barbanson","first_name":"Buys Anton"},{"last_name":"Wellenstein","first_name":"Max D.","full_name":"Wellenstein, Max D."},{"last_name":"Van Oudenaarden","first_name":"Alexander","full_name":"Van Oudenaarden, Alexander"}],"title":"scChIX-seq infers dynamic relationships between histone modifications in single cells","day":"01","_id":"12106","article_processing_charge":"No","oa_version":"Published Version","article_type":"original","scopus_import":"1","intvolume":"        41","department":[{"_id":"ScienComp"}],"publisher":"Springer Nature","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. <i>Nature Biotechnology</i>. 2023;41:813–823. doi:<a href=\"https://doi.org/10.1038/s41587-022-01560-3\">10.1038/s41587-022-01560-3</a>","apa":"Yeung, J., Florescu, M., Zeller, P., De Barbanson, B. A., Wellenstein, M. D., &#38; Van Oudenaarden, A. (2023). scChIX-seq infers dynamic relationships between histone modifications in single cells. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-022-01560-3\">https://doi.org/10.1038/s41587-022-01560-3</a>","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.” <i>Nature Biotechnology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41587-022-01560-3\">https://doi.org/10.1038/s41587-022-01560-3</a>.","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.","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,” <i>Nature Biotechnology</i>, vol. 41. Springer Nature, pp. 813–823, 2023.","mla":"Yeung, Jake, et al. “ScChIX-Seq Infers Dynamic Relationships between Histone Modifications in Single Cells.” <i>Nature Biotechnology</i>, vol. 41, Springer Nature, 2023, pp. 813–823, doi:<a href=\"https://doi.org/10.1038/s41587-022-01560-3\">10.1038/s41587-022-01560-3</a>.","short":"J. Yeung, M. Florescu, P. Zeller, B.A. De Barbanson, M.D. Wellenstein, A. Van Oudenaarden, Nature Biotechnology 41 (2023) 813–823."},"quality_controlled":"1","ddc":["570"],"doi":"10.1038/s41587-022-01560-3","has_accepted_license":"1","page":"813–823","year":"2023","oa":1,"file":[{"date_created":"2023-08-16T11:30:45Z","relation":"main_file","date_updated":"2023-08-16T11:30:45Z","file_name":"2023_NatureBioTech_Yeung.pdf","content_type":"application/pdf","file_size":12040976,"checksum":"668447a1c8d360b68f8aaf9e08ed644f","file_id":"14066","access_level":"open_access","creator":"dernst","success":1}],"language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"isi":1,"month":"06","type":"journal_article","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.","publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"status":"public","volume":41},{"date_published":"2023-02-01T00:00:00Z","file_date_updated":"2023-02-27T07:46:45Z","publication":"Nature Genetics","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"publication_status":"published","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."}],"date_updated":"2025-04-23T08:45:00Z","date_created":"2023-01-12T12:09:09Z","external_id":{"pmid":["36539617"]},"author":[{"full_name":"Zeller, Peter","last_name":"Zeller","first_name":"Peter"},{"orcid":"0000-0003-1732-1559","last_name":"Yeung","first_name":"Jake","id":"123012b2-db30-11eb-b4d8-a35840c0551b","full_name":"Yeung, Jake"},{"first_name":"Helena","last_name":"Viñas Gaza","full_name":"Viñas Gaza, Helena"},{"full_name":"de Barbanson, Buys Anton","first_name":"Buys Anton","last_name":"de Barbanson"},{"first_name":"Vivek","last_name":"Bhardwaj","full_name":"Bhardwaj, Vivek"},{"full_name":"Florescu, Maria","last_name":"Florescu","first_name":"Maria"},{"first_name":"Reinier","last_name":"van der Linden","full_name":"van der Linden, Reinier"},{"full_name":"van Oudenaarden, Alexander","first_name":"Alexander","last_name":"van Oudenaarden"}],"title":"Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis","_id":"12158","article_processing_charge":"No","oa_version":"Published Version","day":"01","intvolume":"        55","department":[{"_id":"ScienComp"}],"article_type":"review","scopus_import":"1","publisher":"Springer Nature","ddc":["570","000"],"quality_controlled":"1","citation":{"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.","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.","mla":"Zeller, Peter, et al. “Single-Cell SortChIC Identifies Hierarchical Chromatin Dynamics during Hematopoiesis.” <i>Nature Genetics</i>, vol. 55, Springer Nature, 2023, pp. 333–45, doi:<a href=\"https://doi.org/10.1038/s41588-022-01260-3\">10.1038/s41588-022-01260-3</a>.","ieee":"P. Zeller <i>et al.</i>, “Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis,” <i>Nature Genetics</i>, vol. 55. Springer Nature, pp. 333–345, 2023.","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. <i>Nature Genetics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41588-022-01260-3\">https://doi.org/10.1038/s41588-022-01260-3</a>","ama":"Zeller P, Yeung J, Viñas Gaza H, et al. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. <i>Nature Genetics</i>. 2023;55:333-345. doi:<a href=\"https://doi.org/10.1038/s41588-022-01260-3\">10.1038/s41588-022-01260-3</a>","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.” <i>Nature Genetics</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41588-022-01260-3\">https://doi.org/10.1038/s41588-022-01260-3</a>."},"doi":"10.1038/s41588-022-01260-3","page":"333-345","has_accepted_license":"1","file":[{"file_id":"12688","access_level":"open_access","creator":"dernst","success":1,"date_created":"2023-02-27T07:46:45Z","relation":"main_file","file_name":"2023_NatureGenetics_Zeller.pdf","date_updated":"2023-02-27T07:46:45Z","checksum":"6fdb8e34fbeea63edd0f2c6c2cc5823e","file_size":21484855,"content_type":"application/pdf"}],"language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2023","oa":1,"month":"02","type":"journal_article","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.","status":"public","publication_identifier":{"issn":["1061-4036"],"eissn":["1546-1718"]},"keyword":["Genetics"],"volume":55}]