{"entity": "researcher", "timestamp": "2026-07-19T06:55:54.406Z", "family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "affiliations": ["Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, Biomedicum, 17177, Stockholm, Sweden. goncalo.castelo-branco@ki.se.", "Ming Wai Lau Centre for Reparative Medicine, Stockholm Node, Karolinska Institutet, 171 77, Stockholm, Sweden. goncalo.castelo-branco@ki.se."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321"}}, "publications": [{"entity": "publication", "iuid": "59eca9ec25b940089924c25b003d94a3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/59eca9ec25b940089924c25b003d94a3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/59eca9ec25b940089924c25b003d94a3"}}, "title": "Single-nucleus epigenomic profiling of the adult human central nervous system unveils epigenetic memory of developmental programs.", "authors": [{"family": "Kabbe", "given": "Mukund", "initials": "M"}, {"family": "Agirre", "given": "Eneritz", "initials": "E", "orcid": "0000-0002-5012-0305", "researcher": {"href": "https://publications.scilifelab.se/researcher/a507b19745c64c3bb8ef5dce800c8687.json"}}, {"family": "Carlstr\u00f6m", "given": "Karl E", "initials": "KE", "orcid": "0000-0002-3001-2403", "researcher": {"href": "https://publications.scilifelab.se/researcher/3aa5f65acad34b5790a2b9f607521825.json"}}, {"family": "Dumral", "given": "\u00d6zge", "initials": "\u00d6", "orcid": "0000-0002-9980-2702", "researcher": {"href": "https://publications.scilifelab.se/researcher/8288edd47f70479e93e1fc441d486997.json"}}, {"family": "Lor", "given": "Yuk Kit", "initials": "YK"}, {"family": "Pohl", "given": "Fabio Baldivia", "initials": "FB", "orcid": "0000-0003-1695-4936", "researcher": {"href": "https://publications.scilifelab.se/researcher/c7913023dd124c8f96f5d072af0eff56.json"}}, {"family": "Ruffin", "given": "Nicolas", "initials": "N", "orcid": "0000-0002-3698-5505", "researcher": {"href": "https://publications.scilifelab.se/researcher/991af3c2719f4c0b9d4feeae24c5161a.json"}}, {"family": "van Bruggen", "given": "David", "initials": "D"}, {"family": "Meijer", "given": "Mandy", "initials": "M"}, {"family": "Seeker", "given": "Luise A", "initials": "LA"}, {"family": "Bestard-Cuche", "given": "Nadine", "initials": "N"}, {"family": "Lederer", "given": "Alex R", "initials": "AR", "orcid": "0000-0001-6381-5088", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa3aa57bbddf4845b2d2c438ecfb2bff.json"}}, {"family": "Zhang", "given": "Jilin", "initials": "J"}, {"family": "Ahola", "given": "Virpi", "initials": "V"}, {"family": "Goldman", "given": "Steven A", "initials": "SA"}, {"family": "Edstr\u00f6m", "given": "Erik", "initials": "E"}, {"family": "Arvidsson", "given": "Lisa", "initials": "L", "orcid": "0000-0003-2129-5357", "researcher": {"href": "https://publications.scilifelab.se/researcher/654ca67f559842669ed19aefa16f878b.json"}}, {"family": "Moreira", "given": "Tiago Holm", "initials": "TH"}, {"family": "Bartosovic", "given": "Marek", "initials": "M", "orcid": "0000-0003-2057-6050", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce3c36916eb844e7bc10f73b95f6494a.json"}}, {"family": "Jagodic", "given": "Maja", "initials": "M", "orcid": "0000-0003-0756-889X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b651ef39c6b0436992e2305f425eba72.json"}}, {"family": "Williams", "given": "Anna", "initials": "A", "orcid": "0000-0002-6329-382X", "researcher": {"href": "https://publications.scilifelab.se/researcher/80c29c92194a4af3a6ed8f9d18dbddfe.json"}}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}], "type": "journal article", "published": "2026-03-19", "journal": {"title": "Nat. Neurosci.", "issn": "1546-1726", "issn-l": "1097-6256"}, "abstract": "Neural cells in the adult human central nervous system (CNS) display extensive transcriptional heterogeneity. How different layers of epigenetic regulation underpin this heterogeneity is poorly understood. Here we profile, at the single-nuclei epigenomic level, distinct regions of the adult human CNS, for chromatin accessibility and simultaneously for the histone modifications H3K27me3 and H3K27ac. We unveil a putative SOX10 enhancer and primed chromatin signatures at HOX loci in spinal-cord-derived human oligodendroglia (OLG) and astrocytes, but not microglia. These signatures in adult OLG were reminiscent of developmental profiles but were decoupled from robust gene expression. Moreover, using high-resolution Micro-C, we show that induced pluripotent stem-cell-derived human OLGs exhibit a HOX chromatin architecture compatible with the primed chromatin in adult OLGs, bearing a strong resemblance not only to OLG developmental architecture but also to high-grade pontine gliomas. Thus, epigenetic memory from developmental states in adult OLG not only enables them to promptly transcribe Hox family genes during regeneration but also makes them susceptible to gliomagenesis.", "doi": "10.1038/s41593-026-02208-0", "pmid": "41857393", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41593-026-02208-0"}], "notes": [], "created": "2026-03-23T13:16:33.192Z", "modified": "2026-03-23T13:16:34.150Z"}, {"entity": "publication", "iuid": "0f47f664e3e4473d9f72b07bc5730cd2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0f47f664e3e4473d9f72b07bc5730cd2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0f47f664e3e4473d9f72b07bc5730cd2"}}, "title": "Distinct radial glia subtypes regulate midbrain dopaminergic neuron development.", "authors": [{"family": "\u00c1sgr\u00edmsd\u00f3ttir", "given": "Emil\u00eda Sif", "initials": "ES", "orcid": "0000-0003-1509-6853", "researcher": {"href": "https://publications.scilifelab.se/researcher/b8fc060425ec4835b3bbef9ef2eb90a1.json"}}, {"family": "Bassini", "given": "Luca Fusar", "initials": "LF", "orcid": "0009-0005-8256-8074", "researcher": {"href": "https://publications.scilifelab.se/researcher/69009a47fd394ed5ac1372076eb1be28.json"}}, {"family": "Sun", "given": "Ting", "initials": "T", "orcid": "0000-0002-7104-7215", "researcher": {"href": "https://publications.scilifelab.se/researcher/521fca43267242fca06da0f5fc823e6a.json"}}, {"family": "Puigsasllosas Pastor", "given": "Cl\u00e0udia", "initials": "C", "orcid": "0009-0007-6498-5223", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ee97e4af1854228ab68a0bc94619ef3.json"}}, {"family": "di Val Cervo", "given": "Pia Rivetti", "initials": "PR", "orcid": "0000-0001-5999-1230", "researcher": {"href": "https://publications.scilifelab.se/researcher/45578a8b146d4eaf8b7f5e1391e6a5e3.json"}}, {"family": "Gyllborg", "given": "Daniel", "initials": "D"}, {"family": "Lee", "given": "Kawai", "initials": "K"}, {"family": "Grigsby", "given": "Christopher L", "initials": "CL", "orcid": "0000-0002-0105-3847", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4407a0f102b4ee596d7944155d9226e.json"}}, {"family": "Jude", "given": "Baptiste", "initials": "B", "orcid": "0000-0002-5506-2482", "researcher": {"href": "https://publications.scilifelab.se/researcher/60e0f4af135c4eff99a95ff1cac825bb.json"}}, {"family": "Abaurre", "given": "Carmen", "initials": "C", "orcid": "0000-0002-7800-2829", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a55672674314bf593124300d5c2840f.json"}}, {"family": "Islam", "given": "Saiful", "initials": "S"}, {"family": "L\u00f6nnerberg", "given": "Peter", "initials": "P"}, {"family": "Villaescusa", "given": "Carlos", "initials": "C"}, {"family": "Salt\u00f3", "given": "Carmen", "initials": "C"}, {"family": "Barker", "given": "Roger A", "initials": "RA", "orcid": "0000-0001-8843-7730", "researcher": {"href": "https://publications.scilifelab.se/researcher/125769a66f77471da6266577717a6395.json"}}, {"family": "Linnarsson", "given": "Sten", "initials": "S", "orcid": "0000-0002-3491-3444", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c0d35942ce042688ea07f23902a8d46.json"}}, {"family": "Castelo-Branco", "given": "Goncalo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}, {"family": "La Manno", "given": "Gioele", "initials": "G", "orcid": "0000-0003-1428-8757", "researcher": {"href": "https://publications.scilifelab.se/researcher/2dab6b6e789a46eba434ceadf38b6601.json"}}, {"family": "Toledo", "given": "Enrique M", "initials": "EM", "orcid": "0000-0002-1460-4708", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa05854e643c499c8efe6781d3457167.json"}}, {"family": "Arenas", "given": "Ernest", "initials": "E", "orcid": "0000-0003-0197-6577", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3bb18ad1c4b4dae99b60ab0ae13e36a.json"}}], "type": "journal article", "published": "2026-02-16", "journal": {"title": "Nat. Neurosci.", "issn": "1546-1726", "issn-l": "1097-6256"}, "abstract": "Understanding the development of midbrain dopaminergic (mesDA) neurons is essential for advancing cell replacement therapies for Parkinson's disease. In the developing ventral midbrain (VM), radial glia (Rgl) cells are the progenitors of mesDA neurons. However, distinct Rgl subtypes have recently been identified, and their individual roles are unclear. Here we analyze transcriptomic data from mouse and human VM Rgl to define their contributions to mesDA neuron development. We identify Rgl1 as the progenitor of the mesDA lineage, and reveal a Rgl1 transcriptional network coordinated by BMAL1, which we validate as a new regulator of mesDA neurogenesis. Moreover, we uncover Rgl3 as a key signaling subtype and show that factors expressed by Rgl3 promote the survival and yield of human stem cell-derived mesDA neurons. Our findings delineate distinct roles of Rgl subtypes, elucidate lineage relationships in the developing VM and uncover new factors that improve the derivation of clinically relevant human mesDA neurons.", "doi": "10.1038/s41593-026-02200-8", "pmid": "41699318", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41593-026-02200-8"}], "notes": [], "created": "2026-02-26T13:31:00.279Z", "modified": "2026-02-26T13:31:01.932Z"}, {"entity": "publication", "iuid": "1e5708bc6c1c4c099e773f1d29e68641", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1e5708bc6c1c4c099e773f1d29e68641.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1e5708bc6c1c4c099e773f1d29e68641"}}, "title": "Anoctamin-2-specific T cells link Epstein-Barr virus to multiple sclerosis.", "authors": [{"family": "Thomas", "given": "Olivia G", "initials": "OG", "orcid": "0000-0002-2011-1344", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea07f812ffee4db893c6f98548563525.json"}}, {"family": "Rykaczewska", "given": "Urszula", "initials": "U"}, {"family": "Gale\u0161i\u0107", "given": "Marina", "initials": "M"}, {"family": "van der Burgt", "given": "Rianne T M", "initials": "RTM"}, {"family": "Hall\u00e9n", "given": "Nils", "initials": "N"}, {"family": "Ferro", "given": "Filippo", "initials": "F", "orcid": "0000-0002-6023-8227", "researcher": {"href": "https://publications.scilifelab.se/researcher/27810903638948feb4391fa537a7eda3.json"}}, {"family": "Bronge", "given": "Mattias", "initials": "M", "orcid": "0000-0002-1258-3982", "researcher": {"href": "https://publications.scilifelab.se/researcher/691b77352a57408896ef1fb486980ccd.json"}}, {"family": "Marti", "given": "Zoe", "initials": "Z"}, {"family": "Li", "given": "Yue", "initials": "Y"}, {"family": "Riqu\u00e9", "given": "Alexandra Hill", "initials": "AH"}, {"family": "Lin", "given": "Jianing", "initials": "J"}, {"family": "Krstic", "given": "Aleksa", "initials": "A"}, {"family": "Gromadzka", "given": "Alicja", "initials": "A"}, {"family": "Szonder", "given": "Andr\u00e1s Levente", "initials": "AL"}, {"family": "Sorini", "given": "Chiara", "initials": "C", "orcid": "0000-0002-6803-8377", "researcher": {"href": "https://publications.scilifelab.se/researcher/975173f37f144f06b236817e224de7f0.json"}}, {"family": "Reina-Campos", "given": "Mar\u00eda", "initials": "M"}, {"family": "Sun", "given": "Ting", "initials": "T", "orcid": "0000-0002-7104-7215", "researcher": {"href": "https://publications.scilifelab.se/researcher/521fca43267242fca06da0f5fc823e6a.json"}}, {"family": "Rubio Rodr\u00edguez-Kirby", "given": "Leslie A", "initials": "LA", "orcid": "0000-0003-4467-2661", "researcher": {"href": "https://publications.scilifelab.se/researcher/9790e215a63d40aa8fac497b537999f9.json"}}, {"family": "Dumral", "given": "\u00d6zge", "initials": "\u00d6", "orcid": "0000-0002-9980-2702", "researcher": {"href": "https://publications.scilifelab.se/researcher/8288edd47f70479e93e1fc441d486997.json"}}, {"family": "Berglund", "given": "Rasmus", "initials": "R"}, {"family": "Kakhki", "given": "Majid Pahlevan", "initials": "MP"}, {"family": "Adzemovic", "given": "Milena Z", "initials": "MZ"}, {"family": "Zeitelhofer", "given": "Manuel", "initials": "M"}, {"family": "Akpinar", "given": "Birce", "initials": "B"}, {"family": "Tengvall", "given": "Katarina", "initials": "K", "orcid": "0000-0003-0424-3571", "researcher": {"href": "https://publications.scilifelab.se/researcher/59b02aaaf03b4cd39150c3034888c81d.json"}}, {"family": "Nilsson", "given": "Ola B", "initials": "OB", "orcid": "0000-0002-7516-1760", "researcher": {"href": "https://publications.scilifelab.se/researcher/096ce3bf888b4ad395d53bb3c11f6946.json"}}, {"family": "Holmgren", "given": "Erik", "initials": "E", "orcid": "0000-0002-2656-1864", "researcher": {"href": "https://publications.scilifelab.se/researcher/6160949c45cf4daaab3991d051db5a16.json"}}, {"family": "Cucuzza", "given": "Chiara Starvaggi", "initials": "CS"}, {"family": "H\u00f6gelin", "given": "Klara Asplund", "initials": "KA"}, {"family": "Gafvelin", "given": "Guro", "initials": "G", "orcid": "0000-0003-1618-4011", "researcher": {"href": "https://publications.scilifelab.se/researcher/870294f4604744ccb212a3c299887ecc.json"}}, {"family": "Fink", "given": "Katharina", "initials": "K"}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}, {"family": "Needhamsen", "given": "Maria", "initials": "M"}, {"family": "Khademi", "given": "Mohsen", "initials": "M", "orcid": "0000-0003-0801-1444", "researcher": {"href": "https://publications.scilifelab.se/researcher/5446d6d754bc4c429d0e48ade419413c.json"}}, {"family": "Piehl", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-8329-5219", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee04062fbee34836a4fa3f4d2e8076cd.json"}}, {"family": "Gr\u00e4slund", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0002-5391-600X", "researcher": {"href": "https://publications.scilifelab.se/researcher/52adbc739e274652bbf877facf4f0959.json"}}, {"family": "Alfredsson", "given": "Lars", "initials": "L", "orcid": "0000-0003-1688-6697", "researcher": {"href": "https://publications.scilifelab.se/researcher/6df230614a8a448e8607e03480169658.json"}}, {"family": "Lund", "given": "Harald", "initials": "H", "orcid": "0000-0001-8046-0805", "researcher": {"href": "https://publications.scilifelab.se/researcher/4fe4902c355449e4812008d4ad7a37e0.json"}}, {"family": "Uhl\u00e9n", "given": "Per", "initials": "P", "orcid": "0000-0003-1446-1062", "researcher": {"href": "https://publications.scilifelab.se/researcher/91c3e953634140b8974186ac0d7eac85.json"}}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Martin", "given": "Roland", "initials": "R"}, {"family": "Jagodic", "given": "Maja", "initials": "M", "orcid": "0000-0003-0756-889X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b651ef39c6b0436992e2305f425eba72.json"}}, {"family": "Gr\u00f6nlund", "given": "Hans", "initials": "H", "orcid": "0000-0003-4882-7624", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e701613f60249b793f2def737168a05.json"}}, {"family": "Guerreiro-Cacais", "given": "Andr\u00e9 Ortlieb", "initials": "AO", "orcid": "0000-0002-4561-2823", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b824181455243b19f4aa145a4545870.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T"}], "type": "journal article", "published": "2026-01-22", "journal": {"title": "Cell", "issn": "1097-4172", "issn-l": "0092-8674", "volume": "189", "issue": "2", "pages": "585-602.e38"}, "abstract": "Epstein-Barr virus (EBV) infection constitutes a prerequisite for multiple sclerosis (MS) development, and cross-reactivity between EBV nuclear antigen 1 (EBNA1) and anoctamin-2 (ANO2) antibodies was previously demonstrated in persons with MS (pwMS). Here, we show that ANO2-specific CD4+ T cells are more frequent in pwMS. Immunization of SJL/J mice with ANO2 or EBNA1 led to cross-reactive CD4+ T cell and antibody responses. ANO2 pre-immunization led to exacerbated experimental autoimmune encephalomyelitis (EAE), an effect mediated by CD4+ T cells, as confirmed by adoptive transfer experiments. T cell clones with cross-reactivity to EBNA1 and ANO2 could be isolated from natalizumab-treated pwMS, and sequencing of EBNA1- and ANO2-specific T cell receptors (TCRs) revealed a significant repertoire overlap. We thus report the first mechanistic evidence that EBNA1 CD4+ T cells can target the MS autoantigen ANO2, thereby establishing a link between EBV infection and neuroinflammation.", "doi": "10.1016/j.cell.2025.12.032", "pmid": "41534529", "labels": {"Autoimmunity and Serology Profiling": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pii", "key": "S0092-8674(25)01481-3"}], "notes": [], "created": "2026-01-15T20:23:02.729Z", "modified": "2026-03-24T09:17:16.086Z"}, {"entity": "publication", "iuid": "cf1b91a85bc74e92ad44a2a472bf97b8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cf1b91a85bc74e92ad44a2a472bf97b8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cf1b91a85bc74e92ad44a2a472bf97b8"}}, "title": "Distinct transcriptomic and epigenomic responses of mature oligodendrocytes during disease progression in a mouse model of multiple sclerosis.", "authors": [{"family": "Zheng", "given": "Chao", "initials": "C"}, {"family": "Herv\u00e9", "given": "Bastien", "initials": "B", "orcid": "0000-0002-2610-8365", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd3c5f38fbf64b30828c15839db38448.json"}}, {"family": "Meijer", "given": "Mandy", "initials": "M"}, {"family": "Rubio Rodr\u00edguez-Kirby", "given": "Leslie Ann", "initials": "LA"}, {"family": "Guerreiro Cacais", "given": "Andr\u00e9 Ortlieb", "initials": "AO", "orcid": "0000-0002-4561-2823", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b824181455243b19f4aa145a4545870.json"}}, {"family": "Kukanja", "given": "Petra", "initials": "P", "orcid": "0000-0003-1228-5923", "researcher": {"href": "https://publications.scilifelab.se/researcher/082ef6e681214c14b8ca36cd0188722b.json"}}, {"family": "Kabbe", "given": "Mukund", "initials": "M"}, {"family": "Jimenez-Beristain", "given": "Tony", "initials": "T", "orcid": "0009-0005-3756-3354", "researcher": {"href": "https://publications.scilifelab.se/researcher/9717ea6f895441649166ea40aa34d2c3.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T"}, {"family": "Agirre", "given": "Eneritz", "initials": "E", "orcid": "0000-0002-5012-0305", "researcher": {"href": "https://publications.scilifelab.se/researcher/a507b19745c64c3bb8ef5dce800c8687.json"}}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}], "type": "journal article", "published": "2025-12-00", "journal": {"title": "Nat. Neurosci.", "issn": "1546-1726", "volume": "28", "issue": "12", "pages": "2612-2627", "issn-l": "1097-6256"}, "abstract": "Multiple sclerosis (MS) is a chronic autoimmune disease that targets mature oligodendrocytes (MOLs) and their myelin. MOLs are heterogeneous and can transition to immune-like states in MS. However, the dynamics of this process remain unclear. Here, we used single-cell multiome assay for transposase-accessible chromatin and RNA sequencing targeting oligodendroglia (OLG) from the experimental autoimmune encephalomyelitis (EAE) MS mouse model at multiple disease stages. We found that immune OLG states appear at early disease stages and persist to late stages, which can be consistent with epigenetic memory of previous neuroinflammation. Transcription factor activity suggested immunosuppression in OLG at early disease stages. Different MOLs exhibit differential responsiveness to EAE, with MOL2 exhibiting a stronger transcriptional immune response than MOL5/MOL6, and showed divergent responses at the epigenetic level during disease evolution. Our single-cell multiomic resource highlights dynamic and subtype-specific responses of OLG to EAE, which might be amenable to modulation in MS.", "doi": "10.1038/s41593-025-02100-3", "pmid": "41249698", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41593-025-02100-3"}], "notes": [], "created": "2025-12-04T08:40:54.011Z", "modified": "2025-12-04T08:40:54.919Z"}, {"entity": "publication", "iuid": "e962bd7ef8824c55975d40adb2d41799", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e962bd7ef8824c55975d40adb2d41799.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e962bd7ef8824c55975d40adb2d41799"}}, "title": "Oligodendroglia as functional effectors of Multiple Sclerosis risk variants", "authors": [{"family": "Carlstr\u00f6m", "given": "Karl E", "initials": "KE", "orcid": "0000-0002-3001-2403", "researcher": {"href": "https://publications.scilifelab.se/researcher/3aa5f65acad34b5790a2b9f607521825.json"}}, {"family": "Agirre", "given": "Eneritz", "initials": "E"}, {"family": "Sun", "given": "Ting", "initials": "T", "orcid": "0000-0002-7104-7215", "researcher": {"href": "https://publications.scilifelab.se/researcher/521fca43267242fca06da0f5fc823e6a.json"}}, {"family": "Dumral", "given": "\u00d6zge", "initials": "\u00d6"}, {"family": "Kabbe", "given": "Mukund", "initials": "M"}, {"family": "Mahmud", "given": "Neemat", "initials": "N"}, {"family": "Kit Lor", "given": "Yuk", "initials": "Y"}, {"family": "Pahlevan Kakhki", "given": "Majid", "initials": "M", "orcid": "0000-0002-5407-3147", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f376c85cfbe4711ae41d9ee5ade8f09.json"}}, {"family": "Khademi", "given": "Mohsen", "initials": "M"}, {"family": "Jagodic", "given": "Maja", "initials": "M"}, {"family": "Goldman", "given": "Steve A", "initials": "SA", "orcid": "0000-0002-5498-4303", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a78fe500aa54369b3716c70792dee90.json"}}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}], "type": "posted-content", "published": "2025-11-12", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.11.11.687640", "pmid": null, "labels": {"CRISPR Functional Genomics": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Short read": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-19T09:35:53.525Z", "modified": "2025-12-18T18:35:03.301Z"}, {"entity": "publication", "iuid": "ce62204de21e4d48a7ac1939f7545c21", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce62204de21e4d48a7ac1939f7545c21.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce62204de21e4d48a7ac1939f7545c21"}}, "title": "Cellular architecture of evolving neuroinflammatory lesions and multiple sclerosis pathology.", "authors": [{"family": "Kukanja", "given": "Petra", "initials": "P", "orcid": "0000-0003-1228-5923", "researcher": {"href": "https://publications.scilifelab.se/researcher/082ef6e681214c14b8ca36cd0188722b.json"}}, {"family": "Langseth", "given": "Christoffer M", "initials": "CM"}, {"family": "Rubio Rodr\u00edguez-Kirby", "given": "Leslie A", "initials": "LA", "orcid": "0000-0003-4467-2661", "researcher": {"href": "https://publications.scilifelab.se/researcher/9790e215a63d40aa8fac497b537999f9.json"}}, {"family": "Agirre", "given": "Eneritz", "initials": "E", "orcid": "0000-0002-5012-0305", "researcher": {"href": "https://publications.scilifelab.se/researcher/a507b19745c64c3bb8ef5dce800c8687.json"}}, {"family": "Zheng", "given": "Chao", "initials": "C"}, {"family": "Raman", "given": "Amitha", "initials": "A"}, {"family": "Yokota", "given": "Chika", "initials": "C"}, {"family": "Avenel", "given": "Christophe", "initials": "C", "orcid": "0000-0002-1835-921X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5471168acdf94b63b1eab431fd1e8442.json"}}, {"family": "Tiklov\u00e1", "given": "Katarina", "initials": "K", "orcid": "0000-0002-9529-4552", "researcher": {"href": "https://publications.scilifelab.se/researcher/14bbad41b8ed42268b71014ce111d247.json"}}, {"family": "Guerreiro-Cacais", "given": "Andr\u00e9 O", "initials": "AO", "orcid": "0000-0002-4561-2823", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b824181455243b19f4aa145a4545870.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T"}, {"family": "Hilscher", "given": "Markus M", "initials": "MM", "orcid": "0000-0001-7782-0830", "researcher": {"href": "https://publications.scilifelab.se/researcher/1de5317c53f34bc89dabfddb0be44983.json"}}, {"family": "Nilsson", "given": "Mats", "initials": "M"}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}], "type": "journal article", "published": "2024-04-11", "journal": {"title": "Cell", "issn": "1097-4172", "issn-l": "0092-8674", "volume": "187", "issue": "8", "pages": "1990-2009.e19"}, "abstract": "Multiple sclerosis (MS) is a neurological disease characterized by multifocal lesions and smoldering pathology. Although single-cell analyses provided insights into cytopathology, evolving cellular processes underlying MS remain poorly understood. We investigated the cellular dynamics of MS by modeling temporal and regional rates of disease progression in mouse experimental autoimmune encephalomyelitis (EAE). By performing single-cell spatial expression profiling using in situ sequencing (ISS), we annotated disease neighborhoods and found centrifugal evolution of active lesions. We demonstrated that disease-associated (DA)-glia arise independently of lesions and are dynamically induced and resolved over the disease course. Single-cell spatial mapping of human archival MS spinal cords confirmed the differential distribution of homeostatic and DA-glia, enabled deconvolution of active and inactive lesions into sub-compartments, and identified new lesion areas. By establishing a spatial resource of mouse and human MS neuropathology at a single-cell resolution, our study unveils the intricate cellular dynamics underlying MS.", "doi": "10.1016/j.cell.2024.02.030", "pmid": "38513664", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Short read": "Service", "BioImage Informatics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative", "In Situ Sequencing": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0092-8674(24)00233-2"}], "notes": [], "created": "2024-04-09T12:34:31.275Z", "modified": "2025-10-17T13:02:16.765Z"}, {"entity": "publication", "iuid": "49729300502940308d16f6e606078065", "links": {"self": {"href": "https://publications.scilifelab.se/publication/49729300502940308d16f6e606078065.json"}, "display": {"href": "https://publications.scilifelab.se/publication/49729300502940308d16f6e606078065"}}, "title": "Single cell-resolutionin situsequencing elucidates spatial dynamics of multiple sclerosis lesion and disease evolution", "authors": [{"family": "Langseth", "given": "C M", "initials": "CM", "orcid": "0000-0003-2230-8594", "researcher": {"href": "https://publications.scilifelab.se/researcher/df19aaf2ad714a63aa40dc6b18a06229.json"}}, {"family": "Kukanja", "given": "P", "initials": "P", "orcid": "0000-0003-1228-5923", "researcher": {"href": "https://publications.scilifelab.se/researcher/082ef6e681214c14b8ca36cd0188722b.json"}}, {"family": "Rubio Rodr\u00edguez-Kirby", "given": "L A", "initials": "LA", "orcid": "0000-0003-4467-2661", "researcher": {"href": "https://publications.scilifelab.se/researcher/9790e215a63d40aa8fac497b537999f9.json"}}, {"family": "Agirre", "given": "E", "initials": "E", "orcid": "0000-0002-5012-0305", "researcher": {"href": "https://publications.scilifelab.se/researcher/a507b19745c64c3bb8ef5dce800c8687.json"}}, {"family": "Raman", "given": "A", "initials": "A"}, {"family": "Yokota", "given": "C", "initials": "C"}, {"family": "Avenel", "given": "C", "initials": "C", "orcid": "0000-0002-1835-921X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5471168acdf94b63b1eab431fd1e8442.json"}}, {"family": "Tiklov\u00e1", "given": "K", "initials": "K", "orcid": "0000-0002-9529-4552", "researcher": {"href": "https://publications.scilifelab.se/researcher/14bbad41b8ed42268b71014ce111d247.json"}}, {"family": "Guerreiro-Cacais", "given": "A O", "initials": "AO", "orcid": "0000-0002-4561-2823", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b824181455243b19f4aa145a4545870.json"}}, {"family": "Olsson", "given": "T", "initials": "T", "orcid": "0000-0002-2938-1877", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd9a20a941214f97a22f010df37cd8e1.json"}}, {"family": "Hilscher", "given": "M M", "initials": "MM", "orcid": "0000-0001-7782-0830", "researcher": {"href": "https://publications.scilifelab.se/researcher/1de5317c53f34bc89dabfddb0be44983.json"}}, {"family": "Nilsson", "given": "M", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}, {"family": "Castelo-Branco", "given": "G", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}], "type": "posted-content", "published": "2023-06-30", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2023.06.29.547074", "pmid": null, "labels": {"Bioinformatics Support for Computational Resources": "Service", "In Situ Sequencing": "Service"}, "xrefs": [], "notes": [], "created": "2023-12-04T09:32:57.399Z", "modified": "2025-12-18T19:49:45.149Z"}, {"entity": "publication", "iuid": "50ebba759c9b46de865a47f18bd85eb2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/50ebba759c9b46de865a47f18bd85eb2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/50ebba759c9b46de865a47f18bd85eb2"}}, "title": "Multimodal chromatin profiling using nanobody-based single-cell CUT&Tag.", "authors": [{"family": "Bartosovic", "given": "Marek", "initials": "M", "orcid": "0000-0003-2057-6050", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce3c36916eb844e7bc10f73b95f6494a.json"}}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}], "type": "journal article", "published": "2023-06-00", "journal": {"title": "Nat. Biotechnol.", "issn": "1546-1696", "volume": "41", "issue": "6", "pages": "794-805", "issn-l": "1087-0156"}, "abstract": "Probing histone modifications at a single-cell level in thousands of cells has been enabled by technologies such as single-cell CUT&Tag. Here we describe nano-CUT&Tag (nano-CT), which allows simultaneous mapping of up to three epigenomic modalities at single-cell resolution using nanobody-Tn5 fusion proteins. Multimodal nano-CT is compatible with starting materials as low as 25,000-200,000 cells and has significantly higher sensitivity and number of fragments per cell than single-cell CUT&Tag. We use nano-CT to simultaneously profile chromatin accessibility, H3K27ac, and H3K27me3 in juvenile mouse brain, allowing for discrimination of more cell types and states than unimodal single-cell CUT&Tag. We also infer chromatin velocity between assay for transposase-accessible chromatin (ATAC) and H3K27ac in the oligodendrocyte lineage and deconvolute H3K27me3 repressive states, finding two sequential waves of H3K27me3 repression at distinct gene modules during oligodendrocyte lineage progression. Given its high resolution, versatility, and multimodal features, nano-CT allows unique insights in epigenetic landscapes in complex biological systems at the single-cell level.", "doi": "10.1038/s41587-022-01535-4", "pmid": "36536148", "labels": {"National Genomics Infrastructure": "Service", "NGI Short read": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10264246"}, {"db": "pii", "key": "10.1038/s41587-022-01535-4"}], "notes": [], "created": "2023-10-04T11:58:23.047Z", "modified": "2024-01-16T13:48:33.301Z"}, {"entity": "publication", "iuid": "52e365acd12b4c318e05d09da7818e98", "links": {"self": {"href": "https://publications.scilifelab.se/publication/52e365acd12b4c318e05d09da7818e98.json"}, "display": {"href": "https://publications.scilifelab.se/publication/52e365acd12b4c318e05d09da7818e98"}}, "title": "Single-cell CUT&Tag profiles histone modifications and transcription factors in complex tissues.", "authors": [{"family": "Bartosovic", "given": "Marek", "initials": "M", "orcid": "0000-0003-2057-6050", "researcher": {"href": "https://publications.scilifelab.se/researcher/ce3c36916eb844e7bc10f73b95f6494a.json"}}, {"family": "Kabbe", "given": "Mukund", "initials": "M"}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}], "type": "journal article", "published": "2021-07-00", "journal": {"title": "Nat. Biotechnol.", "issn": "1546-1696", "issn-l": "1087-0156", "volume": "39", "issue": "7", "pages": "825-835"}, "abstract": "In contrast to single-cell approaches for measuring gene expression and DNA accessibility, single-cell methods for analyzing histone modifications are limited by low sensitivity and throughput. Here, we combine the CUT&Tag technology, developed to measure bulk histone modifications, with droplet-based single-cell library preparation to produce high-quality single-cell data on chromatin modifications. We apply single-cell CUT&Tag (scCUT&Tag) to tens of thousands of cells of the mouse central nervous system and probe histone modifications characteristic of active promoters, enhancers and gene bodies (H3K4me3, H3K27ac and H3K36me3) and inactive regions (H3K27me3). These scCUT&Tag profiles were sufficient to determine cell identity and deconvolute regulatory principles such as promoter bivalency, spreading of H3K4me3 and promoter-enhancer connectivity. We also used scCUT&Tag to investigate the single-cell chromatin occupancy of transcription factor OLIG2 and the cohesin complex component RAD21. Our results indicate that analysis of histone modifications and transcription factor occupancy at single-cell resolution provides unique insights into epigenomic landscapes in the central nervous system.", "doi": "10.1038/s41587-021-00869-9", "pmid": "33846645", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Collaborative", "NGI Stockholm (Genomics Production)": null, "NGI Stockholm (Genomics Applications)": null, "National Genomics Infrastructure": null, "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41587-021-00869-9"}, {"db": "pmc", "key": "PMC7611252"}, {"db": "mid", "key": "EMS118412"}], "notes": [], "created": "2021-04-13T13:18:06.127Z", "modified": "2024-01-16T13:48:39.210Z"}, {"entity": "publication", "iuid": "5c901b5af4f94bdf82bd969d255f0767", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5c901b5af4f94bdf82bd969d255f0767.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5c901b5af4f94bdf82bd969d255f0767"}}, "title": "Distinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury", "authors": [{"family": "Floriddia", "given": "Elisa M", "initials": "EM", "orcid": "0000-0003-2304-8114", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ea55e5ce2b74a799fbcce59b53e62ac.json"}}, {"family": "Louren\u00e7o", "given": "T\u00e2nia", "initials": "T"}, {"family": "Zhang", "given": "Shupei", "initials": "S"}, {"family": "van Bruggen", "given": "David", "initials": "D", "orcid": "0000-0001-6794-7731", "researcher": {"href": "https://publications.scilifelab.se/researcher/d613135b6ba740c59062e3e7e4fd8174.json"}}, {"family": "Hilscher", "given": "Markus M", "initials": "MM", "orcid": "0000-0001-7782-0830", "researcher": {"href": "https://publications.scilifelab.se/researcher/1de5317c53f34bc89dabfddb0be44983.json"}}, {"family": "Kukanja", "given": "Petra", "initials": "P", "orcid": "0000-0003-1228-5923", "researcher": {"href": "https://publications.scilifelab.se/researcher/082ef6e681214c14b8ca36cd0188722b.json"}}, {"family": "Gon\u00e7alves dos Santos", "given": "Jo\u00e3o P", "initials": "JP"}, {"family": "Alt\u0131nk\u00f6k", "given": "M\u00fcge", "initials": "M"}, {"family": "Yokota", "given": "Chika", "initials": "C"}, {"family": "Llorens-Bobadilla", "given": "Enric", "initials": "E", "orcid": "0000-0002-7891-1272", "researcher": {"href": "https://publications.scilifelab.se/researcher/3144601c466246cfa70acbe8c7ee00ee.json"}}, {"family": "Mulinyawe", "given": "Sara B", "initials": "SB"}, {"family": "Gr\u00e3os", "given": "M\u00e1rio", "initials": "M", "orcid": "0000-0002-2707-1488", "researcher": {"href": "https://publications.scilifelab.se/researcher/86454440d6754732b4d8f813d399a9ed.json"}}, {"family": "Sun", "given": "Lu O", "initials": "LO", "orcid": "0000-0002-9293-7241", "researcher": {"href": "https://publications.scilifelab.se/researcher/7bfd19d5fc054ae1a0e6c0c6f286daca.json"}}, {"family": "Fris\u00e9n", "given": "Jonas", "initials": "J"}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}], "type": "journal-article", "published": "2020-11-17", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "5860"}, "abstract": "Mature oligodendrocytes (MOLs) show transcriptional heterogeneity, the functional consequences of which are unclear. MOL heterogeneity might correlate with the local environment or their interactions with different neuron types. Here, we show that distinct MOL populations have spatial preference in the mammalian central nervous system (CNS). We found that MOL type 2 (MOL2) is enriched in the spinal cord when compared to the brain, while MOL types 5 and 6 (MOL5/6) increase their contribution to the OL lineage with age in all analyzed regions. MOL2 and MOL5/6 also have distinct spatial preference in the spinal cord regions where motor and sensory tracts run. OL progenitor cells (OPCs) are not specified into distinct MOL populations during development, excluding a major contribution of OPC intrinsic mechanisms determining MOL heterogeneity. In disease, MOL2 and MOL5/6 present different susceptibility during the chronic phase following traumatic spinal cord injury. Our results demonstrate that the distinct MOL populations have different spatial preference and different responses to disease.", "doi": "10.1038/s41467-020-19453-x", "pmid": "33203872", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Eukaryotic Single Cell Genomics (ESCG)": "Service", "Bioinformatics Support for Computational Resources": "Service", "In Situ Sequencing": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7673029"}, {"db": "pii", "key": "10.1038/s41467-020-19453-x"}], "notes": [], "created": "2020-12-07T16:36:40.432Z", "modified": "2025-10-17T13:02:18.056Z"}, {"entity": "publication", "iuid": "ec6422dbc5dc4b039f6c638f56ddcca9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ec6422dbc5dc4b039f6c638f56ddcca9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ec6422dbc5dc4b039f6c638f56ddcca9"}}, "title": "Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas-Casp8-Bid-axis.", "authors": [{"family": "Carlstr\u00f6m", "given": "Karl E", "initials": "KE"}, {"family": "Zhu", "given": "Keying", "initials": "K", "orcid": "0000-0001-7500-1532", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b85d1ae8136464788be19d62a8863d7.json"}}, {"family": "Ewing", "given": "Ewoud", "initials": "E", "orcid": "0000-0001-8644-366X", "researcher": {"href": "https://publications.scilifelab.se/researcher/aea9350a4f864d8e8781ab111b4f9273.json"}}, {"family": "Krabbendam", "given": "Inge E", "initials": "IE"}, {"family": "Harris", "given": "Robert A", "initials": "RA", "orcid": "0000-0003-4990-509X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b0733d3c25145139f42cad897d6726b.json"}}, {"family": "Falc\u00e3o", "given": "Ana Mendanha", "initials": "AM"}, {"family": "Jagodic", "given": "Maja", "initials": "M"}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}, {"family": "Piehl", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-8329-5219", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee04062fbee34836a4fa3f4d2e8076cd.json"}}], "type": "journal article", "published": "2020-08-13", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4071", "issn-l": "2041-1723"}, "abstract": "Arrest of oligodendrocyte (OL) differentiation and remyelination following myelin damage in multiple sclerosis (MS) is associated with neurodegeneration and clinical worsening. We show that Glutathione S-transferase 4\u03b1 (Gsta4) is highly expressed during adult OL differentiation and that Gsta4 loss impairs differentiation into myelinating OLs in vitro. In addition, we identify Gsta4 as a target of both dimethyl fumarate, an existing MS therapy, and clemastine fumarate, a candidate remyelinating agent in MS. Overexpression of Gsta4 reduces expression of Fas and activity of the mitochondria-associated Casp8-Bid-axis in adult oligodendrocyte precursor cells, leading to improved OL survival during differentiation. The Gsta4 effect on apoptosis during adult OL differentiation was corroborated in vivo in both lysolecithin-induced demyelination and experimental autoimmune encephalomyelitis models, where Casp8 activity was reduced in Gsta4-overexpressing OLs. Our results identify Gsta4 as an intrinsic regulator of OL differentiation, survival and remyelination, as well as a potential target for future reparative MS therapies.", "doi": "10.1038/s41467-020-17871-5", "pmid": "32792491", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-17871-5"}, {"db": "pmc", "key": "PMC7426940"}], "notes": [], "created": "2021-01-08T16:29:42.593Z", "modified": "2024-01-16T13:48:41.933Z"}, {"entity": "publication", "iuid": "30a54de97a514ce29242a464f143a6f9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/30a54de97a514ce29242a464f143a6f9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/30a54de97a514ce29242a464f143a6f9"}}, "title": "Functionally distinct subgroups of oligodendrocyte precursor cells integrate neural activity and execute myelin formation.", "authors": [{"family": "Marisca", "given": "Roberta", "initials": "R"}, {"family": "Hoche", "given": "Tobias", "initials": "T"}, {"family": "Agirre", "given": "Eneritz", "initials": "E", "orcid": "0000-0002-5012-0305", "researcher": {"href": "https://publications.scilifelab.se/researcher/a507b19745c64c3bb8ef5dce800c8687.json"}}, {"family": "Hoodless", "given": "Laura Jane", "initials": "LJ"}, {"family": "Barkey", "given": "Wenke", "initials": "W"}, {"family": "Auer", "given": "Franziska", "initials": "F"}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}, {"family": "Czopka", "given": "Tim", "initials": "T", "orcid": "0000-0002-6824-8112", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a9b1bd37a6a4ec2ac6b236795531d81.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Nat. Neurosci.", "issn": "1546-1726", "volume": "23", "issue": "3", "pages": "363-374", "issn-l": "1097-6256"}, "abstract": "Recent reports have revealed that oligodendrocyte precursor cells (OPCs) are heterogeneous. It remains unclear whether such heterogeneity reflects different subtypes of cells with distinct functions or instead reflects transiently acquired states of cells with the same function. By integrating lineage formation of individual OPC clones, single-cell transcriptomics, calcium imaging and neural activity manipulation, we show that OPCs in the zebrafish spinal cord can be divided into two functionally distinct groups. One subgroup forms elaborate networks of processes and exhibits a high degree of calcium signaling, but infrequently differentiates despite contact with permissive axons. Instead, these OPCs divide in an activity- and calcium-dependent manner to produce another subgroup, with higher process motility and less calcium signaling and that readily differentiates. Our data show that OPC subgroups are functionally diverse in their response to neurons and that activity regulates the proliferation of a subset of OPCs that is distinct from the cells that generate differentiated oligodendrocytes.", "doi": "10.1038/s41593-019-0581-2", "pmid": "32066987", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41593-019-0581-2"}, {"db": "pmc", "key": "PMC7292734"}, {"db": "mid", "key": "EMS85307"}], "notes": [], "created": "2020-07-08T13:05:15.850Z", "modified": "2024-01-16T13:48:42.870Z"}]}