Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis
Open accessAbstract
Impaired function/differentiation of progenitor cells might provide an explanation for the limited remyelination observed in the majority of chronic multiple sclerosis lesions. Here, we establish that in the normal adult human CNS, the transcription factors Nkx2.2 and Olig2 are strongly expressed in progenitor cells while mature oligodendrocytes are characterized by low levels of Olig2 or Nkx2.2. In vitro studies confirmed the expression of Olig2 in oligodendroglial progenitor cells and mature oligodendrocytes while astrocytes, microglial cells and neurons were negative for Olig2. In early multiple sclerosis lesions, we found Olig2-positive progenitor cells throughout all lesion stages and in periplaque white matter (PPWM). The number of progenitors in PPWM was significantly increased compared with the white matter from controls. In chronic multiple sclerosis lesions progenitor cells were still present, however, in significantly lower numbers than in early multiple sclerosis lesions. A subpopulation of progenitor cells in early multiple sclerosis lesions and PPWM but not in control cases co-expressed NogoA, a marker of mature oligodendrocytes. The co-expression of these two markers suggested that these cells were maturing oligodendrocytes recently recruited from the progenitor pool. In contrast, in chronic multiple sclerosis lesions maturing progenitors were only rarely present. In summary, we provide evidence that a differentiation block of oligodendroglial progenitors is a major determinant of remyelination failure in chronic multiple sclerosis lesions.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Non-proliferative Nkx2.2+ precursors with a profile consistent with these cells have been observed in lesions of multiple sclerosis patients.
“Non-proliferative Nkx2.2+ precursors with a profile consistent with these cells (Fig. S10) have been observed in lesions of multiple sclerosis patients (26).”
From Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system (2016) · cites this paper as [26]
The Discussion identifies strongly Nkx2.2-positive cells as progenitors in adult human CNS. The ‘In early multiple sclerosis lesions’ section reports Olig2-positive progenitors in lesions and finds that only rare Olig2-positive cells co-express the proliferation marker Ki67. The lesion and proliferation analyses focused on Olig2, however, so they do not directly establish that the non-proliferative cells observed in lesions were Nkx2.2-positive. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe efficacy of remyelination depends on multiple factors such as age, disease duration and lesion location.
“The efficacy of remyelination has been shown to depend on multiple factors such as, age, disease duration and lesion location.”
From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [14]
The Introduction (page unavailable) contrasts remyelination in early and chronic multiple sclerosis lesions and says that, in most chronic lesions, it is absent or limited to the plaque border. This supports variation with disease stage and within a lesion, but the paper does not establish that remyelination efficacy depends on patient age or anatomical lesion location; its early–chronic comparison also does not establish disease duration as a causal factor. (LLM, conf=0.82)
Experimental — accuracy not yet measuredA block in oligodendrocyte differentiation is a feature of chronic MS lesions.
“Our results showing that M2 cells are required for oligodendrocyte differentiation are of particular interest given that a block in oligodendrocyte differentiation is a feature of chronic MS lesions46.”
From M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination (2013) · cites this paper as [46]
In MS lesions, OPCs are recruited but fail to differentiate into myelinating OLs.
“In MS lesions, OPCs are recruited but fail to differentiate into myelinating OLs, suggesting that remyelination is blocked at the differentiation and remyelination stage rather than during OPC recruitment (Chang et al., 2002; Kuhlmann et al., 2008; Wolswijk, 1998).”
From miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS (2017) · cites this paper as Kuhlmann et al., 2008
In MS, remyelination is blocked at the differentiation/remyelination stage rather than during OPC recruitment.
“In MS lesions, OPCs are recruited but fail to differentiate into myelinating OLs, suggesting that remyelination is blocked at the differentiation and remyelination stage rather than during OPC recruitment (Chang et al., 2002; Kuhlmann et al., 2008; Wolswijk, 1998).”
From miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS (2017) · cites this paper as Kuhlmann et al., 2008
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Relapsing and remitting multiple sclerosis: Pathology of the newly forming lesion
Barnett, M. H., & Prineas, J. W. (2004) · Annals of Neurology · doi:10.1002/ana.20016 · Cited by 1,184 · see citing works
Lu, Q. R., Sun, T., Zhu, Z.-M., Ma, N., García, M., Stiles, C., & Rowitch, D. (2002) · Cell · doi:10.1016/s0092-8674(02)00678-5 · Cited by 1,064 · see citing works
TNFα promotes proliferation of oligodendrocyte progenitors and remyelination
Arnett, H. A., Mason, J., Marino, M., Suzuki, K., Matsushima, G. K., & Ting, J. P.-Y. (2001) · Nature Neuroscience · doi:10.1038/nn738 · Cited by 1,012 · see citing works
Premyelinating Oligodendrocytes in Chronic Lesions of Multiple Sclerosis
Chang, A., Tourtellotte, W. W., Rudick, R., & Trapp, B. D. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa010994 · Cited by 991 · see citing works
Remyelination is extensive in a subset of multiple sclerosis patients
Patrikios, P., Stadelmann, C., Kutzelnigg, A., Rauschka, H., Schmidbauer, M., Laursen, H., Sorensen, P. S., Bruck, W., Lucchinetti, C., & Lassmann, H. (2006) · Brain · doi:10.1093/brain/awl217 · Cited by 807 · see citing works
Self-citation(2006) · Elsevier eBooks · doi:10.1016/b978-0-443-07271-0.x5001-0 · Cited by 769 · see citing works
LINGO-1 negatively regulates myelination by oligodendrocytes
Mi, S., Miller, R. H., Lee, X., Scott, M. L., Shulag-Morskaya, S., Shao, Z., Chang, J., Thill, G., Levesque, M., Zhang, M., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1460 · Cited by 628 · see citing works
Multiple sclerosis: Remyelination of nascent lesions: Remyelination of nascent lesions
Prineas, J. W., Barnard, R. O., Kwon, E. E., Sharer, L. R., & Cho, E. ‐. (1993) · Annals of Neurology · doi:10.1002/ana.410330203 · Cited by 574 · see citing works
Monocyte/macrophage differentiation in early multiple sclerosis lesions
Brück, W., Porada, P., Poser, S., Rieckmann, P., Hanefeld, F., Kretzschmarch, H. A., & Lassmann, H. (1995) · Annals of Neurology · doi:10.1002/ana.410380514 · Cited by 521 · see citing works
Interleukin-1β Promotes Repair of the CNS
Mason, J. L., Suzuki, K., Chaplin, D. D., & Matsushima, G. K. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-18-07046.2001 · Cited by 502 · see citing works
Carson, M. J., Behringer, R. R., Brinster, R. L., & McMorris, F. A. (1993) · Neuron · doi:10.1016/0896-6273(93)90173-o · Cited by 474 · see citing works
A quantitative analysis of oligodendrocytes in multiple sclerosis lesions
Lucchinetti, C., Brück, W., Parisi, J., Scheithauer, B., Rodriguez, M., & Lassmann, H. (1999) · Brain · doi:10.1093/brain/122.12.2279 · Cited by 464 · see citing works
Remyelination in multiple sclerosis
Prineas, J. W., & Connell, F. (1979) · Annals of Neurology · doi:10.1002/ana.410050105 · Cited by 454 · see citing works
Remyelination in multiple sclerosis
Piaton, G., Williams, A., Seilhean, D., & Lubetzki, C. (2009) · Progress in brain research · doi:10.1016/s0079-6123(09)17530-1 · Cited by 440 · see citing works
bHLH Transcription Factor Olig1 Is Required to Repair Demyelinated Lesions in the CNS
Arnett, H. A., Fancy, S. P. J., Alberta, J. A., Zhao, C., Plant, S. R., Kaing, S., Raine, C. S., Rowitch, D. H., Franklin, R. J. M., & Stiles, C. D. (2004) · Science · doi:10.1126/science.1103709 · Cited by 416 · see citing works
Patterns of oligodendroglia pathology in multiple sclerosis
Ozawa, K., Suchanek, G., Breitschopf, H., Br€ck, W., Budka, H., Jellinger, K. A., & Lassmann, H. (1994) · Brain · doi:10.1093/brain/117.6.1311 · Cited by 404 · see citing works
Control of oligodendrocyte differentiation by theNkx2.2homeodomain transcription factor
Qi, Y. B., Cai, J., Wu, Y., Wu, R., Lee, J. D., Fu, H. Q., Rao, M. S., Sussel, L., Rubenstein, J. L. R., & Qiu, M. S. (2001) · Development · doi:10.1242/dev.128.14.2723 · Cited by 356 · see citing works
Kotter, M. R., Zhao, C., van Rooijen, N., & Franklin, R. J. M. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.09.019 · Cited by 331 · see citing works
THE NEUROPATHOLOGY OF MULTIPLE SCLEROSIS
Ludwin, S. K. (2000) · Neuroimaging Clinics of North America · doi:10.1016/s1052-5149(25)00665-3 · Cited by 331 · see citing works
Remyelinated Lesions in Multiple Sclerosis
Barkhof, F., Brück, W., Groot, C. J. A. D., Bergers, E., Hulshof, S. C. J., Geurts, J. J. G., Polman, C. H., & van der Valk, P. (2003) · Archives of Neurology · doi:10.1001/archneur.60.8.1073 · Cited by 328 · see citing works
Remyelination can be extensive in multiple sclerosis despite a long disease course
Patani, R., Balaratnam, M. S., Vora, A., & Reynolds, R. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00805.x · Cited by 315 · see citing works
Charles, P., Hernandez, M. P., Stankoff, B., Aigrot, M. S., Colin, C., Rougon, G., Zalc, B., & Lubetzki, C. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.100076197 · Cited by 306 · see citing works
Fancy, S. P. J., Zhao, C., & Franklin, R. J. M. (2004) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2004.06.015 · Cited by 302 · see citing works
Charles, P. (2002) · Brain · doi:10.1093/brain/awf216 · Cited by 289 · see citing works
Multiple Sclerosis: Remyelination in Acute Lesions
Raine, C. S., & WU, E. (1993) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199305000-00003 · Cited by 285 · see citing works
Levine, J. M., & Reynolds, R. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7224 · Cited by 282 · see citing works
Keirstead, H. S., & Blakemore, W. (1997) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199711000-00003 · Cited by 272 · see citing works
Oligodendrocyte precursor cells in the demyelinated multiple sclerosis spinal cord
Wolswijk, G. (2002) · Brain · doi:10.1093/brain/awf031 · Cited by 268 · see citing works
Multiple sclerosis. Oligodendrocyte survival and proliferation in an active established lesion.
Raine, C. S., Scheinberg, L. C., & Waltz, J. M. (1981) · PubMed · Cited by 264 · see citing works
FTY720 modulates human oligodendrocyte progenitor process extension and survival
Miron, V. E., Jung, C., Kim, H. J., Kennedy, T. E., Soliven, B. C., & Antel, J. P. (2007) · Annals of Neurology · doi:10.1002/ana.21227 · Cited by 255 · see citing works
Self-citationLassmann, H., Raine, C. S., Antel, J. P., & Prineas, J. W. (1998) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(98)00031-9 · Cited by 250 · see citing works
Self-citationProtocols for Neural Cell Culture
FEDOROFF, S., & Richardson, A. K. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90164-h · Cited by 249 · see citing works
A role for TGF-beta in oligodendrocyte differentiation.
McKinnon, R. D., Piras, G., Ida, J. A., & Dubois-Dalcq, M. (1993) · The Journal of cell biology · doi:10.1083/jcb.121.6.1397 · Cited by 248 · see citing works
Nishiyama, A., Lin, X., Giese, N. A., Heldin, C., & Stallcup, W. B. (1996) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19960201)43:3 · Cited by 239 · see citing works
Oligodendrocyte survival, loss and birth in lesions of chronic-stage multiple sclerosis
Wolswijk, G. (2000) · Brain · doi:10.1093/brain/123.1.105 · Cited by 238 · see citing works
Development of NG2 neural progenitor cells requires Olig gene function
Ligon, K., Kesari, S., Kitada, M., Sun, T., Arnett, H., Alberta, J., Anderson, D. J., Stiles, C., & Rowitch, D. (2006) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0511001103 · Cited by 225 · see citing works
Oligodendrocytes in the early course of multiple sclerosis
Brück, W., Schmied, M., Suchanek, G., Brück, Y., Breitschopf, H., Poser, S., Piddlesden, S., & Lassmann, H. (1994) · Annals of Neurology · doi:10.1002/ana.410350111 · Cited by 216 · see citing works
Mason, J. L., Toews, A., Hostettler, J. D., Morell, P., Suzuki, K., Goldman, J. E., & Matsushima, G. K. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63726-1 · Cited by 212 · see citing works
Synantocytes: New functions for novel NG2 expressing glia
Butt, A. M., Kiff, J., Hubbard, P. S., & Berry, M. (2002) · Journal of Neurocytology · doi:10.1023/a:1025751900356 · Cited by 202 · see citing works
Efficient central nervous system remyelination requires T cells
Bieber, A. J., Kerr, S., & Rodriguez, M. (2003) · Annals of Neurology · doi:10.1002/ana.10578 · Cited by 196 · see citing works
The response of NG2-expressing oligodendrocyte progenitors to demyelination in MOG-EAE and MS
Reynolds, R., Dawson, M., Papadopoulos, D., Polito, A., di Bello, I. C., Pham-Dinh, D., & Levine, J. (2002) · Journal of Neurocytology · doi:10.1023/a:1025747832215 · Cited by 175 · see citing works
Inflammation stimulates myelination by transplanted oligodendrocyte precursor cells
Setzu, A., Lathia, J. D., Zhao, C., Wells, K., Rao, M. S., ffrench‐Constant, C., & Franklin, R. J. M. (2006) · Glia · doi:10.1002/glia.20371 · Cited by 171 · see citing works
Penderis, J., Shields, S. A., & Franklin, R. J. M. (2003) · Brain · doi:10.1093/brain/awg126 · Cited by 129 · see citing works
Wilson, H., Scolding, N. J., & Raine, C. S. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.04.014 · Cited by 122 · see citing works
Kitada, M., & Rowitch, D. (2006) · Glia · doi:10.1002/glia.20354 · Cited by 121 · see citing works
Copray, S. C. V. M., Balasubramaniyan, V., Levenga, J., de Bruijn, J., Liem, R. S. B., & Boddeke, E. (2005) · Stem Cells · doi:10.1634/stemcells.2005-0239 · Cited by 116 · see citing works
Targett, M. P., Sussmant, J., Scoldingt, N., O'Leary, M. T., Compston, D. A. S., & Blakemore, W. F. (1996) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1996.tb00895.x · Cited by 104 · see citing works
Blaschuk, K., Frost, E. E., & ffrench‐Constant, C. (2000) · Development · doi:10.1242/dev.127.9.1961 · Cited by 102 · see citing works
Kuhlmann, T., Remington, L. T., Maruschak, B., Owens, T., & Brück, W. (2007) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000248559.83573.71 · Cited by 98 · see citing works
Self-citationSimvastatin regulates oligodendroglial process dynamics and survival
Miron, V. E., Rajasekharan, S., Jarjour, A. A., Zamvil, S. S., Kennedy, T. E., & Antel, J. P. (2006) · Glia · doi:10.1002/glia.20441 · Cited by 91 · see citing works
Self-citationTransient upregulation of Nkx2.2 expression in oligodendrocyte lineage cells during remyelination
Watanabe, M., Hadzic, T., & Nishiyama, A. (2004) · Glia · doi:10.1002/glia.20006 · Cited by 82 · see citing works
Identification of glial cell proliferation in early multiple sclerosis lesions
Schönrock, Kuhlmann, Adler, Bitsch, V., & Brück (1998) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.1998.00131.x · Cited by 81 · see citing works
Culture of Glial Cells from Human Brain Biopsies
Yong, V. W., & Antel, J. P. (1997) · Humana Press eBooks · doi:10.1007/978-1-4757-2586-5_11 · Cited by 71 · see citing works
Self-citationChari, D. M., Zhao, C., Kotter, M., Blakemore, W. F., & Franklin, R. J. M. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20763 · Cited by 66 · see citing works
Distinctive Properties of Human Adult Brain-Derived Myelin Progenitor Cells
Ruffini, F., Arbour, N., Blain, M., Olivier, A., & Antel, J. P. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63266-x · Cited by 62 · see citing works
Self-citationResistance of human adult oligodendrocytes to AMPA/kainate receptor-mediated glutamate injury
Wosik, K. (2004) · Brain · doi:10.1093/brain/awh302 · Cited by 54 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- D'Souza SD, Alinauskas KA, Antel JP. Ciliary neurotrophic factor selec- tively protects human oligodendrocytes from tumor necrosis factor- mediated injury. J Neurosci Res 1996; 43: 289-98.
- Qi Y, Cai J, Wu Y, Wu R, Lee J, Fu H, et al. Control of oligodendrocyte differentiation by the Nkx2.2 homeodomain transcription factor. Development 2001; 128: 2723-33.
Cited by
Sorted by citations
M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination
Miron, V. E., Boyd, A., Zhao, J.-W., Yuen, T. J., Ruckh, J. M., Shadrach, J. L., van Wijngaarden, P., Wagers, A. J., Williams, A., Franklin, R. J. M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3469 · Cited by 1,788 · see citing works
Self-citationRemyelination in the CNS: from biology to therapy
Franklin, R. J. M., & ffrench-Constant, C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2480 · Cited by 1,544 · see citing works
Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system
Marques, S., Zeisel, A., Codeluppi, S., van Bruggen, D., Mendanha Falcão, A., Xiao, L., Li, H., Häring, M., Hochgerner, H., Romanov, R. A., et al. (2016) · Science · doi:10.1126/science.aaf6463 · Cited by 1,246 · see citing works
Oligodendrocytes: biology and pathology
Bradl, M., & Lassmann, H. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0601-5 · Cited by 933 · see citing works
An updated histological classification system for multiple sclerosis lesions
Kuhlmann, T., Ludwin, S., Prat, A., Antel, J., Brück, W., & Lassmann, H. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1653-y · Cited by 692 · see citing works
Self-citationMultiple sclerosis progression: time for a new mechanism-driven framework
Kuhlmann, T., Moccia, M., Coetzee, T., Cohen, J. A., Correale, J., Graves, J., Marrie, R. A., Montalban, X., Yong, V. W., Thompson, A. J., et al. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00289-7 · Cited by 667 · see citing works
Self-citationRejuvenation of Regeneration in the Aging Central Nervous System
Ruckh, J. M., Zhao, J.-W., Shadrach, J. L., van Wijngaarden, P., Rao, T. N., Wagers, A. J., & Franklin, R. J. M. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2011.11.019 · Cited by 649 · see citing works
Regenerating CNS myelin — from mechanisms to experimental medicines
Franklin, R. J. M., & ffrench-Constant, C. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.136 · Cited by 647 · see citing works
Oligodendrocytes in development, myelin generation and beyond
Kuhn, S., Gritti, L., Crooks, D., & Dombrowski, Y. (2019) · Cells · doi:10.3390/cells8111424 · Cited by 625 · see citing works
Pathophysiology of the brain extracellular matrix: a new target for remyelination
Lau, L. W., Cua, R., Keough, M. B., Haylock-Jacobs, S., & Yong, V. W. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3550 · Cited by 549 · see citing works
Metformin restores CNS remyelination capacity by rejuvenating aged stem cells
Neumann, B., Baror, R., Zhao, C., Segel, M., Dietmann, S., Rawji, K. S., Foerster, S., McClain, C. R., Chalut, K., van Wijngaarden, P., et al. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.08.015 · Cited by 449 · see citing works
Oligodendrocyte-Encoded HIF Function Couples Postnatal Myelination and White Matter Angiogenesis
Yuen, T. J., Silbereis, J. C., Griveau, A., Chang, S. M., Daneman, R., Fancy, S. P. J., Zahed, H., Maltepe, E., & Rowitch, D. H. (2014) · Cell · doi:10.1016/j.cell.2014.04.052 · Cited by 433 · see citing works
Dynamics of oligodendrocyte generation in multiple sclerosis
Yeung, M. S. Y., Djelloul, M., Steiner, E., Bernard, S., Salehpour, M., Possnert, G., Brundin, L., & Frisén, J. (2019) · Nature · doi:10.1038/s41586-018-0842-3 · Cited by 376 · see citing works
Axin2 as regulatory and therapeutic target in newborn brain injury and remyelination
Fancy, S. P. J., Harrington, E. P., Yuen, T. J., Silbereis, J. C., Zhao, C., Baranzini, S. E., Bruce, C. C., Otero, J. J., Huang, E. J., Nusse, R., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2855 · Cited by 349 · see citing works
Inflammation, demyelination, and degeneration — Recent insights from MS pathology
Stadelmann, C., Wegner, C., & Brück, W. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.07.007 · Cited by 276 · see citing works
Self-citationCortical remyelination: A new target for repair therapies in multiple sclerosis
Chang, A., Staugaitis, S. M., Dutta, R., Batt, C. E., Easley, K. E., Chomyk, A. M., Yong, V. W., Fox, R. J., Kidd, G. J., & Trapp, B. D. (2012) · Annals of Neurology · doi:10.1002/ana.23693 · Cited by 216 · see citing works
Baer, A. S., Syed, Y. A., Kang, S. U., Mitteregger, D., Vig, R., ffrench-Constant, C., Franklin, R. J. M., Altmann, F., Lubec, G., & Kotter, M. R. (2009) · Brain · doi:10.1093/brain/awn334 · Cited by 211 · see citing works
Mechanisms of white matter damage in multiple sclerosis
Lassmann, H. (2014) · Glia · doi:10.1002/glia.22597 · Cited by 191 · see citing works
Kremer, D., Schichel, T., Förster, M., Tzekova, N., Bernard, C., van der Valk, P., van Horssen, J., Hartung, H., Perron, H., & Küry, P. (2013) · Annals of Neurology · doi:10.1002/ana.23970 · Cited by 178 · see citing works
miR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS
Wang, H., Moyano, A. L., Ma, Z., Deng, Y., Lin, Y., Zhao, C., Zhang, L., Jiang, M., He, X., Ma, Z., et al. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.03.001 · Cited by 174 · see citing works
Oligodendroglia and Myelin in Neurodegenerative Diseases: More Than Just Bystanders?
Ettle, B., Schlachetzki, J. C. M., & Winkler, J. (2016) · Molecular Neurobiology · doi:10.1007/s12035-015-9205-3 · Cited by 160 · see citing works
Inhibition of CNS Remyelination by the Presence of Semaphorin 3A
Syed, Y. A., Hand, E., Möbius, W., Zhao, C., Hofer, M., Nave, K. A., & Kotter, M. R. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4930-10.2011 · Cited by 134 · see citing works
Progesterone and Nestorone Facilitate Axon Remyelination: A Role for Progesterone Receptors
Hussain, R., El-Etr, M., Gaci, O., Rakotomamonjy, J., Macklin, W. B., Kumar, N., Sitruk-Ware, R., Schumacher, M., & Ghoumari, A. M. (2011) · Endocrinology · doi:10.1210/en.2011-1219 · Cited by 123 · see citing works
Extracellular Vesicles in Brain Tumors and Neurodegenerative Diseases
Ciregia, F., Urbani, A., & Palmisano, G. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00276 · Cited by 110 · see citing works
Premyelinating Oligodendrocytes: Mechanisms Underlying Cell Survival and Integration
Hughes, E. G., & Stockton, M. E. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.714169 · Cited by 98 · see citing works
Oligodendrocyte progenitor cells in Alzheimer's disease: from physiology to pathology
Zou, P., Wu, C., Liu, T. C.-Y., Duan, R., & Yang, L. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00385-7 · Cited by 97 · see citing works
Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system
Gonzalez, G. A., Hofer, M. P., Syed, Y. A., Amaral, A. I., Rundle, J., Rahman, S., Zhao, C., & Kotter, M. R. N. (2016) · Scientific Reports · doi:10.1038/srep31599 · Cited by 82 · see citing works
Höftberger, R., Fink, S., Aboul‐Enein, F., Botond, G., Olah, J., Berki, T., Ovadi, J., Lassmann, H., Budka, H., & Kovacs, G. G. (2010) · Glia · doi:10.1002/glia.21054 · Cited by 79 · see citing works
Starost, L., Lindner, M., Herold, M., Xu, Y. K. T., Drexler, H. C. A., Heß, K., Ehrlich, M., Ottoboni, L., Ruffini, F., Stehling, M., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02217-8 · Cited by 79 · see citing works
Self-citationPentón-Rol, G., Marín-Prida, J., & McCarty, M. F. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210408123807 · Cited by 73 · see citing works
Syed, Y. A., Baer, A., Hofer, M. P., González, G. A., Rundle, J., Myrta, S., Huang, J. K., Zhao, C., Rossner, M. J., Trotter, M. W. B., et al. (2013) · EMBO Molecular Medicine · doi:10.1002/emmm.201303123 · Cited by 58 · see citing works
Intracellular alpha-synuclein affects early maturation of primary oligodendrocyte progenitor cells
Ettle, B., Reiprich, S., Deusser, J., Schlachetzki, J. C. M., Xiang, W., Prots, I., Masliah, E., Winner, B., Wegner, M., & Winkler, J. (2014) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2014.06.012 · Cited by 57 · see citing works
Baror, R., Neumann, B., Segel, M., Chalut, K. J., Fancy, S. P. J., Schafer, D. P., & Franklin, R. J. M. (2019) · Glia · doi:10.1002/glia.23612 · Cited by 54 · see citing works
Pentón-Rol, G., Marín-Prida, J., & Falcón-Cama, V. (2018) · Behavioral Sciences · doi:10.3390/bs8010015 · Cited by 50 · see citing works
Mozafari, S., Starost, L., Manot-Saillet, B., Garcia-Diaz, B., Xu, Y. K. T., Roussel, D., Levy, M. J. F., Ottoboni, L., Kim, K.-P., Schöler, H. R., et al. (2020) · Science Advances · doi:10.1126/sciadv.abc6983 · Cited by 45 · see citing works
Self-citationDefaux, A., Zurich, M.-G., Honegger, P., & Monnet-Tschudi, F. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.04.053 · Cited by 40 · see citing works
Dziedzic, A., Miller, E., Saluk-Bijak, J., & Bijak, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051852 · Cited by 38 · see citing works
CRISPR-edited human ES-derived oligodendrocyte progenitor cells improve remyelination in rodents
Wagstaff, L. J., Bestard-Cuche, N., Kaczmarek, M., Fidanza, A., McNeil, L., Franklin, R. J. M., & Williams, A. C. (2024) · Nature Communications · doi:10.1038/s41467-024-52444-w · Cited by 30 · see citing works
BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis
Bergner, C. G., van der Meer, F., Franz, J., Vakrakou, A., Würfel, T., Nessler, S., Schäfer, L., Nau-Gietz, C., Winkler, A., Lagumersindez-Denis, N., et al. (2025) · Brain · doi:10.1093/brain/awae293 · Cited by 16 · see citing works
“…in human brain tissue from patients with MS. 19-21 In addition, birth dating of oligodendrocytes by analysis of integrated nuclear bomb test-derived 14 C revealed that few oligodendrocytes were newly generated in shadow plaques of MS patients, supporting the notion that adult oligodendrocytes are…”
Sarrazin, N., Chavret-Reculon, E., Bachelin, C., Felfli, M., Arab, R., Gilardeau, S., Brazhnikova, E., Dubus, E., Yahia Cherif, L., Lorenceau, J., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2115973119 · Cited by 15 · see citing works
Microglial states associate with lesion dynamics in multiple sclerosis
van den Bosch, A. M. R., Khoo, J. H., Lu, Z., Liang, H., Wever, D., Pu, L., Eggen, B. J. L., Uhlén, M., Smolders, J., Hamann, J., et al. (2026) · Cell Reports · doi:10.1016/j.celrep.2026.117538 · Cited by 6 · see citing works
- Authors
- Kuhlmann, T., Miron, V., Cuo, Q., Wegner, C., Antel, J., & Bruck, W.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-05-30
- Volume
- 131
- Issue
- 7
- Pages
- 1749-1758
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2062326815
- Cited by
- 864
- References
- 57
- Citations by year
- 2026: 27 · 2025: 42 · 2024: 48 · 2023: 40 · 2022: 54 · 2021: 64 · 2020: 60 · 2019: 66 · 2018: 53 · 2017: 64 · 2016: 50 · 2015: 56 · 2014: 43 · 2013: 53 · 2012: 33
- FWCI
- 26.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion)
- Funders
- Multiple Sclerosis Society of Canada
- Multiple Sclerosis Society
- European Commission (LSHM‐CT‐2005–018637)
- Directorate for Biological Sciences
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- multiple sclerosis, remyelination failure, Olig2, Nkx2.2, differentiation block, oligodendrocyte maturation, Nogo-A, transcription factors
- MeSH terms
- Oligodendrocyte Transcription Factor 2, Homeobox Protein Nkx-2.2, Adult, Cell Differentiation, Cells, Cultured, Chronic Disease, Female, Humans, Male, Multiple Sclerosis, Myelin Sheath, Nerve Regeneration, Nerve Tissue Proteins, Nuclear Proteins, Oligodendroglia, Retrospective Studies, Stem Cells, Transcription Factors, Homeodomain Proteins, Disease Progression, Zebrafish Proteins, Basic Helix-Loop-Helix Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
