{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:13:11Z","timestamp":1785247991918,"version":"3.55.0"},"reference-count":104,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Start2Cure Foundation","award":["project 0-TI-01"],"award-info":[{"award-number":["project 0-TI-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Multiple sclerosis (MS) is a highly heterogeneous disease, with varying remyelination potential across individuals and between lesions. However, the molecular mechanisms underlying the potential to remyelinate remain poorly understood. In this study, we aimed to take advantage of the intrinsic heterogeneity in remyelinating capacity between MS donors and lesions to uncover known and novel pro-remyelinating molecules for MS therapies.<\/jats:p>\n               <jats:p>To elucidate distinct molecular signatures underlying the potential to remyelinate, we stratified MS donors from the Netherlands Brain Bank cohort (n = 239), based on proportions of remyelinated lesions (RLs), into efficiently remyelinating donors (ERDs; n = 21) and poorly remyelinating donors (PRDs; n = 19). We performed bulk RNA sequencing of RLs, active lesions with ramified and amoeboid microglia\/macrophage morphology (ALs non-foamy), active lesions with foamy microglia\/macrophage morphology (ALs foamy) and normal-appearing white matter (NAWM) from ERDs and PRDs.<\/jats:p>\n               <jats:p>We found that ALs non-foamy were positively correlated with remyelination, whereas ALs foamy were not, indicating a role for microglia\/macrophage state in influencing remyelination potential. Bioinformatics analyses were performed to identify key pathways and molecules implicated in the remyelination process. We found distinct differences between the donors with differing remyelination potential in comparable MS lesion types. The RLs and ALs non-foamy of ERDs versus PRDs showed upregulation of the epithelial\u2013mesenchymal transition pathway, whereas in ALs foamy of PRDs, inflammation and damage-associated pathways (i.e. MTORC1 signalling, TNF signalling and oxidative phosphorylation) were upregulated in comparison to ALs foamy of ERDs, suggesting that these latter pathways might counteract remyelination. We found genes significantly upregulated in RLs and\/or ALs non-foamy of ERDs that have previously been associated with remyelination, including CXCL12, EGF, HGF, IGF2, IL10, PDGFB, PPARG and TREM2, illustrating the strength of our donor and lesion stratification. TGFB1, TGFB2, EGF and IGF1 were determined to be key upstream regulators of genes upregulated in RLs and ALs non-foamy of ERDs. We also identified potential novel pro-remyelinating molecules, such as BTC, GDF10, GDF15, CCN1, CCN4, FGF5, FGF10 and INHBB.<\/jats:p>\n               <jats:p>Our study identified both known and novel genes associated with efficient remyelination that might facilitate the development of therapeutic strategies to promote tissue repair and clinical recovery in MS.<\/jats:p>","DOI":"10.1093\/brain\/awae414","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T18:13:04Z","timestamp":1735063984000},"page":"2201-2217","source":"Crossref","is-referenced-by-count":18,"title":["Distinct transcriptional changes distinguish efficient and poor remyelination in multiple sclerosis"],"prefix":"10.1093","volume":"148","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2296-2396","authenticated-orcid":false,"given":"J Q Alida","family":"Chen","sequence":"first","affiliation":[{"name":"Neuroimmunology Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niamh B","family":"McNamara","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik J","family":"Engelenburg","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Jongejan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam Public Health, Amsterdam University Medical Center , Amsterdam 1105 AZ ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis D","family":"Wever","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaya","family":"Hopman","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esm\u00e9e","family":"van Rixel","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J H","family":"Nijhuis","sequence":"additional","affiliation":[{"name":"Neuroregeneration Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"de Winter","sequence":"additional","affiliation":[{"name":"Neuroregeneration Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry D","family":"Moerland","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam Public Health, Amsterdam University Medical Center , Amsterdam 1105 AZ ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9766-8661","authenticated-orcid":false,"given":"Joost","family":"Smolders","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]},{"name":"Departments of Neurology and Immunology, MS Center ErasMS, Erasmus Medical Center , Rotterdam 1105 BA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost","family":"Verhaagen","sequence":"additional","affiliation":[{"name":"Neuroregeneration Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9448-1727","authenticated-orcid":false,"given":"J\u00f6rg","family":"Hamann","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]},{"name":"Department of Experimental Immunology, Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam University Medical Center , Amsterdam 1105 AZ ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Huitinga","sequence":"additional","affiliation":[{"name":"Neuroimmunology Research Group, Netherlands Institute for Neuroscience , Amsterdam 1105 BA ,","place":["The Netherlands"]},{"name":"Swammerdam Institute for Life Sciences, Center for Neuroscience, University of Amsterdam , Amsterdam 1090 GE ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"2025060300225579000_awae414-B1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0165-5728(98)00031-9","article-title":"Immunopathology of multiple sclerosis: Report on an international meeting held at the Institute of Neurology of the University of Vienna","volume":"86","author":"Lassmann","year":"1998","journal-title":"J Neuroimmunol"},{"key":"2025060300225579000_awae414-B2","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s00401-018-1818-y","article-title":"Progressive multiple sclerosis patients show substantial lesion activity that correlates with clinical disease severity and sex: A retrospective autopsy cohort analysis","volume":"135","author":"Luchetti","year":"2018","journal-title":"Acta Neuropathol"},{"key":"2025060300225579000_awae414-B3","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q","article-title":"Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination","volume":"47","author":"Lucchinetti","year":"2000","journal-title":"Ann Neurol"},{"key":"2025060300225579000_awae414-B4","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/nrn.2017.136","article-title":"Regenerating CNS myelin\u2014From mechanisms to experimental medicines","volume":"18","author":"Franklin","year":"2017","journal-title":"Nat Rev Neurosci"},{"key":"2025060300225579000_awae414-B5","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1016\/j.neuron.2022.09.023","article-title":"CNS remyelination and inflammation: From basic mechanisms to therapeutic opportunities","volume":"110","author":"Franklin","year":"2022","journal-title":"Neuron"},{"key":"2025060300225579000_awae414-B6","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/S1474-4422(20)30140-X","article-title":"Remyelination in multiple sclerosis: From basic science to clinical translation","volume":"19","author":"Lubetzki","year":"2020","journal-title":"Lancet Neurol"},{"key":"2025060300225579000_awae414-B7","doi-asserted-by":"crossref","first-page":"14128","DOI":"10.1523\/JNEUROSCI.3491-13.2014","article-title":"Adult neural precursor cells from the subventricular zone contribute significantly to oligodendrocyte regeneration and remyelination","volume":"34","author":"Xing","year":"2014","journal-title":"J Neurosci"},{"key":"2025060300225579000_awae414-B8","doi-asserted-by":"crossref","first-page":"e29996","DOI":"10.7554\/eLife.29996","article-title":"Transient hypothyroidism favors oligodendrocyte generation providing functional remyelination in the adult mouse brain","volume":"6","author":"Remaud","year":"2017","journal-title":"Elife"},{"key":"2025060300225579000_awae414-B9","doi-asserted-by":"crossref","first-page":"E11807","DOI":"10.1073\/pnas.1808064115","article-title":"The adult oligodendrocyte can participate in remyelination","volume":"115","author":"Duncan","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025060300225579000_awae414-B10","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0022-510X(88)90214-6","article-title":"Myelination by oligodendrocytes isolated from 4\u20136-week-old rat central nervous system and transplanted into newborn shiverer brain","volume":"88","author":"Lubetzki","year":"1988","journal-title":"J Neurol Sci"},{"key":"2025060300225579000_awae414-B11","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41593-021-01009-x","article-title":"New oligodendrocytes exhibit more abundant and accurate myelin regeneration than those that survive demyelination","volume":"25","author":"Neely","year":"2022","journal-title":"Nat Neurosci"},{"key":"2025060300225579000_awae414-B12","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jns.2005.03.008","article-title":"Mechanisms of CNS remyelination\u2014The key to therapeutic advances","volume":"233","author":"Zhao","year":"2005","journal-title":"J Neurol Sci"},{"key":"2025060300225579000_awae414-B13","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1038\/nn1938","article-title":"A functional role for EGFR signaling in myelination and remyelination","volume":"10","author":"Aguirre","year":"2007","journal-title":"Nat Neurosci"},{"key":"2025060300225579000_awae414-B14","doi-asserted-by":"crossref","first-page":"106","DOI":"10.3389\/fnmol.2017.00106","article-title":"EGF enhances oligodendrogenesis from glial progenitor cells","volume":"10","author":"Yang","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"2025060300225579000_awae414-B15","doi-asserted-by":"crossref","first-page":"e41869","DOI":"10.7554\/eLife.41869","article-title":"Circulating transforming growth factor-\u03b21 facilitates remyelination in the adult central nervous system","volume":"8","author":"Hamaguchi","year":"2019","journal-title":"Elife"},{"key":"2025060300225579000_awae414-B16","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1002\/eji.200425430","article-title":"TGF-\u03b2-treated microglia induce oligodendrocyte precursor cell chemotaxis through the HGF-c-Met pathway","volume":"35","author":"Lalive","year":"2005","journal-title":"Eur J Immunol"},{"key":"2025060300225579000_awae414-B17","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/nn.3469","article-title":"M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination","volume":"16","author":"Miron","year":"2013","journal-title":"Nat Neurosci"},{"key":"2025060300225579000_awae414-B18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/135245859700300210","article-title":"Growth factors and myelin regeneration in multiple sclerosis","volume":"3","author":"Webster","year":"1997","journal-title":"Mult Scler"},{"key":"2025060300225579000_awae414-B19","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.mcn.2003.10.014","article-title":"Platelet-derived growth factor regulates oligodendrocyte progenitor numbers in adult CNS and their response following CNS demyelination","volume":"25","author":"Woodruff","year":"2004","journal-title":"Mol Cell Neurosci"},{"key":"2025060300225579000_awae414-B20","doi-asserted-by":"crossref","first-page":"e55149","DOI":"10.1371\/journal.pone.0055149","article-title":"PDGF is required for remyelination-promoting IgM stimulation of oligodendrocyte progenitor cell proliferation","volume":"8","author":"Watzlawik","year":"2013","journal-title":"PLoS One"},{"key":"2025060300225579000_awae414-B21","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mcn.2006.05.009","article-title":"Anosmin-1 modulates the FGF-2-dependent migration of oligodendrocyte precursors in the developing optic nerve","volume":"33","author":"Bribi\u00e1n","year":"2006","journal-title":"Mol Cell Neurosci"},{"key":"2025060300225579000_awae414-B22","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.3390\/biomedicines10112724","article-title":"Exogenous FGF-1 differently regulates oligodendrocyte replenishment in an SCI repair model and cultured cells","volume":"10","author":"Lee","year":"2022","journal-title":"Biomedicines"},{"key":"2025060300225579000_awae414-B23","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.expneurol.2006.12.013","article-title":"CNTF promotes the survival and differentiation of adult spinal cord-derived oligodendrocyte precursor cells in vitro but fails to promote remyelination in vivo","volume":"204","author":"Talbott","year":"2007","journal-title":"Exp Neurol"},{"key":"2025060300225579000_awae414-B24","doi-asserted-by":"crossref","first-page":"7088","DOI":"10.1523\/JNEUROSCI.0487-18.2018","article-title":"Targeting TrkB with a brain-derived neurotrophic factor mimetic promotes myelin repair in the brain","volume":"38","author":"Fletcher","year":"2018","journal-title":"J Neurosci"},{"key":"2025060300225579000_awae414-B25","first-page":"4374","article-title":"CXCL12 induces migration of oligodendrocyte precursor cells through the CXCR4-activated MEK\/ERK and PI3K\/AKT pathways","volume":"18","author":"Tian","year":"2018","journal-title":"Mol Med Rep"},{"issue":"Pt 10","key":"2025060300225579000_awae414-B26","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1093\/brain\/awm202","article-title":"Semaphorin 3A and 3F: Key players in myelin repair in multiple sclerosis?","volume":"130","author":"Williams","year":"2007","journal-title":"Brain"},{"key":"2025060300225579000_awae414-B27","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1007\/s00401-020-02193-z","article-title":"TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis","volume":"140","author":"Cignarella","year":"2020","journal-title":"Acta Neuropathol"},{"key":"2025060300225579000_awae414-B28","doi-asserted-by":"crossref","first-page":"e20210227","DOI":"10.1084\/jem.20210227","article-title":"TREM2-dependent lipid droplet biogenesis in phagocytes is required for remyelination","volume":"218","author":"Gouna","year":"2021","journal-title":"J Exp Med"},{"key":"2025060300225579000_awae414-B29","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/NEN.0000000000000149","article-title":"Activation status of human microglia is dependent on lesion formation stage and remyelination in multiple sclerosis","volume":"74","author":"Peferoen","year":"2015","journal-title":"J Neuropathol Exp Neurol"},{"key":"2025060300225579000_awae414-B30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s41232-022-00193-y","article-title":"Central nervous system regeneration: The roles of glial cells in the potential molecular mechanism underlying remyelination","volume":"42","author":"Quan","year":"2022","journal-title":"Inflamm Regen"},{"key":"2025060300225579000_awae414-B31","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/s41582-019-0184-2","article-title":"The pro-remyelination properties of microglia in the central nervous system","volume":"15","author":"Lloyd","year":"2019","journal-title":"Nat Rev Neurol"},{"issue":"Pt 2","key":"2025060300225579000_awae414-B32","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/brain\/awh707","article-title":"Myelin-laden macrophages are anti-inflammatory, consistent with foam cells in multiple sclerosis","volume":"129","author":"Boven","year":"2006","journal-title":"Brain"},{"key":"2025060300225579000_awae414-B33","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s00401-014-1310-2","article-title":"Macrophage subsets and microglia in multiple sclerosis","volume":"128","author":"Bogie","year":"2014","journal-title":"Acta Neuropathol"},{"key":"2025060300225579000_awae414-B34","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3389\/fphar.2019.00286","article-title":"Targeting microglia and macrophages: A potential treatment strategy for multiple sclerosis","volume":"10","author":"Wang","year":"2019","journal-title":"Front Pharmacol"},{"key":"2025060300225579000_awae414-B35","doi-asserted-by":"crossref","first-page":"e1154","DOI":"10.1212\/NXI.0000000000001154","article-title":"Neurofilament light chain levels in multiple sclerosis correlate with lesions containing foamy macrophages and with acute axonal damage","volume":"9","author":"van den Bosch","year":"2022","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2025060300225579000_awae414-B36","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1523\/JNEUROSCI.22-07-02451.2002","article-title":"The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation","volume":"22","author":"Sim","year":"2002","journal-title":"J Neurosci"},{"issue":"Pt 12","key":"2025060300225579000_awae414-B37","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1093\/brain\/awl217","article-title":"Remyelination is extensive in a subset of multiple sclerosis patients","volume":"129","author":"Patrikios","year":"2006","journal-title":"Brain"},{"key":"2025060300225579000_awae414-B38","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/j.1365-2990.2007.00805.x","article-title":"Remyelination can be extensive in multiple sclerosis despite a long disease course","volume":"33","author":"Patani","year":"2007","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2025060300225579000_awae414-B39","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s00401-020-02189-9","article-title":"Lesion stage-dependent causes for impaired remyelination in MS","volume":"140","author":"He\u00df","year":"2020","journal-title":"Acta Neuropathol"},{"key":"2025060300225579000_awae414-B40","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00401-016-1653-y","article-title":"An updated histological classification system for multiple sclerosis lesions","volume":"133","author":"Kuhlmann","year":"2017","journal-title":"Acta Neuropathol"},{"key":"2025060300225579000_awae414-B41","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1046\/j.1365-2990.2000.00217.x","article-title":"Staging of multiple sclerosis (MS) lesions: Pathology of the time frame of MS","volume":"26","author":"Van Der Valk","year":"2000","journal-title":"Neuropathol Appl Neurobiol"},{"key":"2025060300225579000_awae414-B42","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.biopsych.2023.04.020","article-title":"Microglia transcriptional profiling in major depressive disorder shows inhibition of cortical gray matter microglia","volume":"94","author":"Scheepstra","year":"2023","journal-title":"Biol Psychiatry"},{"key":"2025060300225579000_awae414-B43","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/s41586-019-1404-z","article-title":"Neuronal vulnerability and multilineage diversity in multiple sclerosis","volume":"573","author":"Schirmer","year":"2019","journal-title":"Nature"},{"key":"2025060300225579000_awae414-B44","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/s41586-021-03892-7","article-title":"A lymphocyte\u2013microglia\u2013astrocyte axis in chronic active multiple sclerosis","volume":"597","author":"Absinta","year":"2021","journal-title":"Nature"},{"key":"2025060300225579000_awae414-B45","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neuron.2015.11.013","article-title":"Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse","volume":"89","author":"Zhang","year":"2016","journal-title":"Neuron"},{"key":"2025060300225579000_awae414-B46","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nn.3599","article-title":"Identification of a unique TGF-\u03b2-dependent molecular and functional signature in microglia","volume":"17","author":"Butovsky","year":"2014","journal-title":"Nat Neurosci"},{"key":"2025060300225579000_awae414-B47","doi-asserted-by":"crossref","first-page":"eaam7816","DOI":"10.1126\/scitranslmed.aam7816","article-title":"BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions","volume":"9","author":"Fard","year":"2017","journal-title":"Sci Transl Med"},{"key":"2025060300225579000_awae414-B48","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1038\/s41467-022-30032-0","article-title":"Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination","volume":"13","author":"Ghorbani","year":"2022","journal-title":"Nat Commun"},{"key":"2025060300225579000_awae414-B49","doi-asserted-by":"crossref","first-page":"8321","DOI":"10.1523\/JNEUROSCI.1377-20.2021","article-title":"mTOR signaling regulates metabolic function in oligodendrocyte precursor cells and promotes efficient brain remyelination in the cuprizone model","volume":"41","author":"Jeffries","year":"2021","journal-title":"J Neurosci"},{"key":"2025060300225579000_awae414-B50","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.bbadis.2015.10.010","article-title":"Molecular alterations of the blood\u2013brain barrier under inflammatory conditions: The role of endothelial to mesenchymal transition","volume":"1862","author":"Derada Troletti","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"2025060300225579000_awae414-B51","doi-asserted-by":"crossref","first-page":"14535","DOI":"10.1002\/jcp.28160","article-title":"The basics of epithelial\u2013mesenchymal transition (EMT): A study from a structure, dynamics, and functional perspective","volume":"234","author":"Das","year":"2019","journal-title":"J Cell Physiol"},{"key":"2025060300225579000_awae414-B52","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1016\/j.cell.2021.04.003","article-title":"A cellular and spatial map of the choroid plexus across brain ventricles and ages","volume":"184","author":"Dani","year":"2021","journal-title":"Cell"},{"key":"2025060300225579000_awae414-B53","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/glia.20841","article-title":"Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis","volume":"57","author":"Bai","year":"2009","journal-title":"Glia"},{"key":"2025060300225579000_awae414-B54","doi-asserted-by":"crossref","first-page":"257","DOI":"10.4067\/S0716-97602012000300007","article-title":"Adult mesenchymal stem cell therapy for myelin repair in multiple sclerosis","volume":"45","author":"Rivera","year":"2012","journal-title":"Biol Res"},{"key":"2025060300225579000_awae414-B55","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/ana.21076","article-title":"Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis","volume":"61","author":"Gerdoni","year":"2007","journal-title":"Ann Neurol"},{"key":"2025060300225579000_awae414-B56","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1182\/blood-2005-04-1496","article-title":"Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy","volume":"106","author":"Zappia","year":"2005","journal-title":"Blood"},{"key":"2025060300225579000_awae414-B57","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3390\/brainsci8060111","article-title":"Emerging cellular and molecular strategies for enhancing central nervous system (CNS) remyelination","volume":"8","author":"Abu-Rub","year":"2018","journal-title":"Brain Sci"},{"key":"2025060300225579000_awae414-B58","doi-asserted-by":"crossref","first-page":"3574","DOI":"10.1093\/brain\/awaa333","article-title":"Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis","volume":"143","author":"Petrou","year":"2020","journal-title":"Brain"},{"key":"2025060300225579000_awae414-B59","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1002\/cm.21263","article-title":"Cytoskeletal signaling in TGF\u03b2-induced epithelial\u2013mesenchymal transition","volume":"72","author":"Nalluri","year":"2015","journal-title":"Cytoskeleton (Hoboken)"},{"key":"2025060300225579000_awae414-B60","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.devcel.2015.06.011","article-title":"CNS myelin wrapping is driven by actin disassembly","volume":"34","author":"Zuchero","year":"2015","journal-title":"Dev Cell"},{"key":"2025060300225579000_awae414-B61","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.devcel.2015.05.013","article-title":"Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system","volume":"34","author":"Nawaz","year":"2015","journal-title":"Dev Cell"},{"key":"2025060300225579000_awae414-B62","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.3390\/ijms21031062","article-title":"A role of microtubules in oligodendrocyte differentiation","volume":"21","author":"Lee","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2025060300225579000_awae414-B63","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cell.2019.08.025","article-title":"The Golgi outpost protein TPPP nucleates microtubules and is critical for myelination","volume":"179","author":"Fu","year":"2019","journal-title":"Cell"},{"key":"2025060300225579000_awae414-B64","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s40478-019-0855-7","article-title":"Molecular signature of different lesion types in the brain white matter of patients with progressive multiple sclerosis","volume":"7","author":"Elkjaer","year":"2019","journal-title":"Acta Neuropathol Commun"},{"key":"2025060300225579000_awae414-B65","doi-asserted-by":"crossref","first-page":"7917","DOI":"10.1523\/JNEUROSCI.0363-14.2014","article-title":"TGF\u03b2 signaling regulates the timing of CNS myelination by modulating oligodendrocyte progenitor cell cycle exit through SMAD3\/4\/FoxO1\/Sp1","volume":"34","author":"Palazuelos","year":"2014","journal-title":"J Neurosci"},{"key":"2025060300225579000_awae414-B66","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41586-022-05534-y","article-title":"Microglia regulate central nervous system myelin growth and integrity","volume":"613","author":"McNamara","year":"2023","journal-title":"Nature"},{"key":"2025060300225579000_awae414-B67","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.4049\/jimmunol.164.6.3207","article-title":"TGF-\u03b22 reduces demyelination, virus antigen expression, and macrophage recruitment in a viral model of multiple sclerosis","volume":"164","author":"Drescher","year":"2000","journal-title":"J Immunol"},{"key":"2025060300225579000_awae414-B68","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.1172\/JCI92387","article-title":"Neural precursor cell-secreted TGF-\u03b22 redirects inflammatory monocyte-derived cells in CNS autoimmunity","volume":"127","author":"De Feo","year":"2017","journal-title":"J Clin Invest"},{"key":"2025060300225579000_awae414-B69","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3727\/000000004783984043","article-title":"The effects of transforming growth factor-\u03b22 on dopaminergic graft survival","volume":"13","author":"Macauley","year":"2004","journal-title":"Cell Transplant"},{"key":"2025060300225579000_awae414-B70","doi-asserted-by":"crossref","first-page":"11092","DOI":"10.1523\/JNEUROSCI.2981-05.2005","article-title":"Overexpression of the epidermal growth factor receptor confers migratory properties to nonmigratory postnatal neural progenitors","volume":"25","author":"Aguirre","year":"2005","journal-title":"J Neurosci"},{"key":"2025060300225579000_awae414-B71","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s10571-020-00989-x","article-title":"Epidermal growth factor in the CNS: A beguiling journey from integrated cell biology to multiple sclerosis. An extensive translational overview","volume":"42","author":"Scalabrino","year":"2022","journal-title":"Cell Mol Neurobiol"},{"key":"2025060300225579000_awae414-B72","first-page":"333","article-title":"EGF-coupled gold nanoparticles increase the expression of CNPase and the myelin-associated proteins MAG, MOG, and MBP in the septal nucleus demyelinated by cuprizone","volume":"12","author":"Lira-Diaz","year":"2022","journal-title":"Life (Basel)"},{"key":"2025060300225579000_awae414-B73","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jneuroim.2019.05.006","article-title":"Prevention of clinical and histological signs of MOG-induced experimental allergic encephalomyelitis by prolonged treatment with recombinant human EGF","volume":"332","author":"Nicoletti","year":"2019","journal-title":"J Neuroimmunol"},{"key":"2025060300225579000_awae414-B74","doi-asserted-by":"crossref","first-page":"a021873","DOI":"10.1101\/cshperspect.a021873","article-title":"TGF-\u03b2 and the TGF-\u03b2 family: Context-dependent roles in cell and tissue physiology","volume":"8","author":"Morikawa","year":"2016","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"2025060300225579000_awae414-B75","doi-asserted-by":"crossref","first-page":"F1000 Faculty Rev-2270","DOI":"10.12688\/f1000research.9025.1","article-title":"EGF receptor ligands: Recent advances","volume":"5","author":"Singh","year":"2016","journal-title":"F1000Res"},{"key":"2025060300225579000_awae414-B76","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.tibs.2008.07.006","article-title":"The CCN family of proteins: Structure\u2013function relationships","volume":"33","author":"Holbourn","year":"2008","journal-title":"Trends Biochem Sci"},{"key":"2025060300225579000_awae414-B77","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.tig.2004.08.007","article-title":"Evolution of the Fgf and Fgfr gene families","volume":"20","author":"Itoh","year":"2004","journal-title":"Trends Genet"},{"key":"2025060300225579000_awae414-B78","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3389\/fendo.2018.00117","article-title":"IGF-binding proteins: Why do they exist and why are there so many?","volume":"9","author":"Allard","year":"2018","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2025060300225579000_awae414-B79","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/glia.23119","article-title":"Betacellulin regulates Schwann cell proliferation and myelin formation in the injured mouse peripheral nerve","volume":"65","author":"Valli\u00e8res","year":"2017","journal-title":"Glia"},{"key":"2025060300225579000_awae414-B80","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s10020-021-00292-5","article-title":"Betacellulin regulates peripheral nerve regeneration by affecting Schwann cell migration and axon elongation","volume":"27","author":"Wang","year":"2021","journal-title":"Mol Med"},{"key":"2025060300225579000_awae414-B81","doi-asserted-by":"crossref","first-page":"e13150","DOI":"10.1111\/bpa.13150","article-title":"Quantitative magnetic resonance imaging reflects different levels of histologically determined myelin densities in multiple sclerosis, including remyelination in inactive multiple sclerosis lesions","volume":"33","author":"Wiggermann","year":"2023","journal-title":"Brain Pathol"},{"key":"2025060300225579000_awae414-B82","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1007\/s00401-018-1813-3","article-title":"Activin receptors regulate the oligodendrocyte lineage in health and disease","volume":"135","author":"Dillenburg","year":"2018","journal-title":"Acta Neuropathol"},{"key":"2025060300225579000_awae414-B83","doi-asserted-by":"crossref","first-page":"12269","DOI":"10.1073\/pnas.1918196117","article-title":"Activin-A limits Th17 pathogenicity and autoimmune neuroinflammation via CD39 and CD73 ectonucleotidases and Hif1-\u03b1-dependent pathways","volume":"117","author":"Morianos","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025060300225579000_awae414-B84","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1016\/j.cub.2007.07.019","article-title":"Activin-\u03b2A signaling is required for zebrafish fin regeneration","volume":"17","author":"Ja\u017awi\u0144ska","year":"2007","journal-title":"Curr Biol"},{"key":"2025060300225579000_awae414-B85","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1242\/dev.168708","article-title":"Combinatorial actions of Tgf\u03b2 and activin ligands promote oligodendrocyte development and CNS myelination","volume":"145","author":"Dutta","year":"2018","journal-title":"Development"},{"key":"2025060300225579000_awae414-B86","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.ydbio.2005.06.012","article-title":"BMP-3 is a novel inhibitor of both activin and BMP-4 signaling in Xenopus embryos","volume":"285","author":"Gamer","year":"2005","journal-title":"Dev Biol"},{"key":"2025060300225579000_awae414-B87","doi-asserted-by":"crossref","first-page":"7934","DOI":"10.1074\/jbc.M209710200","article-title":"Inhibin is an antagonist of bone morphogenetic protein signaling","volume":"278","author":"Wiater","year":"2003","journal-title":"J Biol Chem"},{"issue":"Pt 3","key":"2025060300225579000_awae414-B88","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.expneurol.2016.02.007","article-title":"Molecular, cellular and functional events in axonal sprouting after stroke","volume":"287","author":"Carmichael","year":"2017","journal-title":"Exp Neurol"},{"key":"2025060300225579000_awae414-B89","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1038\/nn.4146","article-title":"GDF10 is a signal for axonal sprouting and functional recovery after stroke","volume":"18","author":"Li","year":"2015","journal-title":"Nat Neurosci"},{"key":"2025060300225579000_awae414-B90","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/nrd.2015.27","article-title":"Stroke: GDF10 spurs on axonal sprouting after stroke","volume":"15","author":"Kingwell","year":"2016","journal-title":"Nat Rev Drug Discov"},{"key":"2025060300225579000_awae414-B91","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00441-015-2219-3","article-title":"Growth\/differentiation factor-15 and its role in peripheral nervous system lesion and regeneration","volume":"362","author":"Wang","year":"2015","journal-title":"Cell Tissue Res"},{"key":"2025060300225579000_awae414-B92","doi-asserted-by":"crossref","first-page":"e675","DOI":"10.1212\/NXI.0000000000000675","article-title":"Growth differentiation factor 15 is increased in stable MS","volume":"7","author":"Amstad","year":"2020","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2025060300225579000_awae414-B93","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.immuni.2015.01.020","article-title":"Emerging functions of amphiregulin in orchestrating immunity, inflammation, and tissue repair","volume":"42","author":"Zaiss","year":"2015","journal-title":"Immunity"},{"key":"2025060300225579000_awae414-B94","doi-asserted-by":"crossref","first-page":"10762","DOI":"10.1073\/pnas.1509070112","article-title":"IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin\u2013EGFR interactions","volume":"112","author":"Monticelli","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025060300225579000_awae414-B95","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1126\/science.abq4822","article-title":"Droplet-based forward genetic screening of astrocyte\u2013microglia cross-talk","volume":"379","author":"Wheeler","year":"2023","journal-title":"Science"},{"key":"2025060300225579000_awae414-B96","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1111\/cns.14176","article-title":"FGF\/FGFR system in the central nervous system demyelinating disease: Recent progress and implications for multiple sclerosis","volume":"29","author":"Zhang","year":"2023","journal-title":"CNS Neurosci Ther"},{"key":"2025060300225579000_awae414-B97","doi-asserted-by":"crossref","first-page":"884","DOI":"10.3390\/cells10040884","article-title":"FGF\/FGFR pathways in multiple sclerosis and in its disease models","volume":"10","author":"Rajendran","year":"2021","journal-title":"Cells"},{"key":"2025060300225579000_awae414-B98","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s40478-014-0168-9","article-title":"Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination","volume":"2","author":"Mohan","year":"2014","journal-title":"Acta Neuropathol Commun"},{"key":"2025060300225579000_awae414-B99","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3389\/fncel.2020.00237","article-title":"FGF5 regulates Schwann cell migration and adhesion","volume":"14","author":"Chen","year":"2020","journal-title":"Front Cell Neurosci"},{"key":"2025060300225579000_awae414-B100","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.3389\/fphar.2019.01224","article-title":"FGF10 enhances peripheral nerve regeneration via the preactivation of the PI3K\/Akt signaling-mediated antioxidant response","volume":"10","author":"Dong","year":"2019","journal-title":"Front Pharmacol"},{"key":"2025060300225579000_awae414-B101","doi-asserted-by":"crossref","first-page":"19869","DOI":"10.1038\/srep19869","article-title":"Neuron-derived FGF10 ameliorates cerebral ischemia injury via inhibiting NF-\u03baB-dependent neuroinflammation and activating PI3K\/Akt survival signaling pathway in mice","volume":"6","author":"Li","year":"2016","journal-title":"Sci Rep"},{"key":"2025060300225579000_awae414-B102","doi-asserted-by":"crossref","first-page":"2625","DOI":"10.1093\/cvr\/cvab340","article-title":"FGF10 promotes cardiac repair through a dual cellular mechanism increasing cardiomyocyte renewal and inhibiting fibrosis","volume":"118","author":"Hubert","year":"2022","journal-title":"Cardiovasc Res"},{"key":"2025060300225579000_awae414-B103","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.3390\/ijms22094340","article-title":"Targeting CCN proteins in rheumatoid arthritis and osteoarthritis","volume":"22","author":"Macdonald","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2025060300225579000_awae414-B104","doi-asserted-by":"crossref","first-page":"4195","DOI":"10.1002\/jcp.30171","article-title":"Emerging role of CCN family proteins in fibrosis","volume":"236","author":"Sun","year":"2021","journal-title":"J Cell Physiol"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awae414\/61272312\/awae414.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/148\/6\/2201\/61272312\/awae414.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/148\/6\/2201\/61272312\/awae414.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T04:23:35Z","timestamp":1748924615000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/148\/6\/2201\/7932175"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,24]]},"references-count":104,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,12,24]]},"published-print":{"date-parts":[[2025,6,3]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awae414","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2024,12,24]]}}}