NG2 glia generate new oligodendrocytes but few astrocytes in a murine experimental autoimmune encephalomyelitis model of demyelinating disease
Open accessAbstract
The adult mammalian brain and spinal cord contain glial precursors that express platelet-derived growth factor receptor α subunit (PDGFRA) and the NG2 proteoglycan. These "NG2 cells" descend from oligodendrocyte precursors in the perinatal CNS and continue to generate myelinating oligodendrocytes in the gray and white matter of the postnatal brain. It has been proposed that NG2 cells can also generate reactive astrocytes at sites of CNS injury or demyelination. To test this we examined the fates of PDGFRA/NG2 cells in the mouse spinal cord during experimental autoimmune encephalomyelitis (EAE)--a demyelinating condition that models some aspects of multiple sclerosis in humans. We administered tamoxifen to Pdgfra-CreER(T2):Rosa26R-YFP mice to induce yellow fluorescent protein (YFP) expression in PDGFRA/NG2 cells and their differentiated progeny. We subsequently induced EAE and observed a large (>4-fold) increase in the local density of YFP(+) cells, >90% of which were oligodendrocyte lineage cells. Many of these became CC1-positive, NG2-negative differentiated oligodendrocytes that expressed myelin markers CNP and Tmem10/Opalin. PDGFRA/NG2 cells generated very few GFAP(+)-reactive astrocytes (1-2% of all YFP(+) cells) or NeuN(+) neurons (<0.02%). Thus, PDGFRA/NG2 cells act predominantly as a reservoir of new oligodendrocytes in the demyelinated spinal cord.
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?
At P120+7, 19.9% ± 3.2% of all optic nerve OPs (defined by NG2 immunolabeling) were YFP labeled, less than in adult corpus callosum (approximately 45%) or spinal cord (approximately 39%).
“A short time later (P120+7), 19.9% ± 3.2% of all optic nerve OPs (defined by NG2 immunolabeling) were YFP labeled (mean ±SD, n = 3 mice), less than in the adult corpus callosum (∼45%; Rivers et al., 2008) or spinal cord (∼39%; Zawadzka et al., 2010; Tripathi et al., 2010).”
From Oligodendrocyte Dynamics in the Healthy Adult CNS: Evidence for Myelin Remodeling (2013) · cites this paper as Tripathi et al., 2010
The Materials and Methods section (Induction of EAE; page unavailable) reports that about 30% of spinal-cord PDGFRA+ cells became YFP+, compared with about 45–50% in the adult forebrain. This supports the regional comparison but not the cited ∼39% spinal-cord figure, and the paper measures PDGFRA+ rather than NG2-immunolabeled cells for that comparison. The 19.9% optic-nerve result is presented as the citing authors’ own finding, not as a result attributed to Tripathi et al. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe Cre/lox system has been used in reporter mice to track oligodendrogenesis and myelin synthesis during development, after CNS demyelination, and after SCI.
“The Cre/lox system been used in reporter mice to track oligodendrogenesis and myelin synthesis during development [45, 81], after CNS demyelination [82, 83], and after SCI [44, 84, 85].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [83]
The Discussion reports using Cre-lox reporter mice to track new oligodendrocytes in an EAE demyelination model. But the Results state that the reporter did not label myelin sheaths and the authors could not determine whether the new oligodendrocytes formed myelin. The development and SCI portions of the sentence are attached to other citations. (LLM, conf=0.90)
Experimental — accuracy not yet measured
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
Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus
Srinivas, S., Watanabe, T., Lin, C.-S., William, C. M., Tanabe, Y., Jessell, T. M., & Costantini, F. (2001) · BMC Developmental Biology · doi:10.1186/1471-213x-1-4 · Cited by 3,121 · see citing works
RAFF, M. C., Miller, R. H., & Noble, M. (1983) · Nature · doi:10.1038/303390a0 · Cited by 2,030 · see citing works
PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice
Rivers, L. E., Young, K. M., Rizzi, M., Jamen, F., Psachoulia, K., Wade, A., Kessaris, N., & Richardson, W. D. (2008) · Nature Neuroscience · doi:10.1038/nn.2220 · Cited by 961 · see citing works
Self-citationDawson, M. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(03)00210-0 · Cited by 927 · see citing works
Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity
Nishiyama, A., Komitova, M., Suzuki, R., & Zhu, X. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2495 · Cited by 865 · see citing works
Proliferation and Differentiation of Progenitor Cells Throughout the Intact Adult Rat Spinal Cord
Horner, P. J., Power, A. E., Kempermann, G., Kuhn, H. G., Palmer, T. D., Winkler, J., Thal, L. J., & Gage, F. H. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-06-02218.2000 · Cited by 777 · see citing works
Malatesta, P., Hack, M. A., Hartfuss, E., Kettenmann, H., Klinkert, W. E. F., Kirchhoff, F., & Götz, M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00116-8 · Cited by 744 · see citing works
NG2 cells generate both oligodendrocytes and gray matter astrocytes
Zhu, X., Bergles, D. E., & Nishiyama, A. (2007) · Development · doi:10.1242/dev.004895 · Cited by 678 · see citing works
Zawadzka, M., Rivers, L. E., Fancy, S. P. J., Zhao, C., Tripathi, R., Jamen, F., Young, K., Goncharevich, A., Pohl, H., Rizzi, M., et al. (2010) · Cell stem cell · doi:10.1016/j.stem.2010.04.002 · Cited by 650 · see citing works
Self-citationDimou, L., Simon, C., Kirchhoff, F., Takebayashi, H., & Götz, M. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2831-08.2008 · Cited by 551 · see citing works
Endogenous progenitors remyelinate demyelinated axons in the adult CNS
Gensert, J. M., & Goldman, J. E. (1997) · Neuron · doi:10.1016/s0896-6273(00)80359-1 · Cited by 544 · see citing works
Identification of an adult-specific glial progenitor cell
Wolswijk, G., & Noble, M. A. (1989) · Development · doi:10.1242/dev.105.2.387 · Cited by 485 · see citing works
Dayer, A. G., Cleaver, K. M., Abouantoun, T. J., & Cameron, H. A. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200407053 · Cited by 454 · see citing works
Pringle, N. P., Mudhar, H. S., Collarini, E. J., & Richardson, W. D. (1992) · Development · doi:10.1242/dev.115.2.535 · Cited by 442 · see citing works
Self-citationProliferating bipotential glial progenitor cells in adult rat optic nerve
ffrench‐Constant, C., & RAFF, M. C. (1986) · Nature · doi:10.1038/319499a0 · Cited by 385 · see citing works
NG2+ Glial Cells: A Novel Glial Cell Population in the Adult Brain
Nishiyama, A., Chang, A., & Trapp, B. D. (1999) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199911000-00001 · Cited by 297 · see citing works
Differentiation of proliferated NG2-positive glial progenitor cells in a remyelinating lesion
Watanabe, M., Toyama, Y., & Nishiyama, A. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10338 · Cited by 261 · see citing works
Fate of endogenous stem/progenitor cells following spinal cord injury
Horky, L. L., Galimi, F., Gage, F. H., & Horner, P. J. (2006) · Journal of Comparative Neurology · doi:10.1002/cne.21065 · Cited by 258 · see citing works
Cell cycle dynamics of NG2 cells in the postnatal and ageing brain
Psachoulia, K., Jamen, F., Young, K. M., & Richardson, W. D. (2009) · Neuron Glia Biology · doi:10.1017/s1740925x09990354 · Cited by 257 · see citing works
Polito, A., & Reynolds, R. (2005) · Journal of Anatomy · doi:10.1111/j.1469-7580.2005.00454.x · Cited by 231 · 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
Aguirre, A. A., & Gallo, V. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.3572-04.2004 · Cited by 224 · see citing works
Hall, A. C., Giese, N. A., & Richardson, W. D. (1996) · Development · doi:10.1242/dev.122.12.4085 · Cited by 211 · see citing works
Self-citationSynantocytes: the fifth element
Butt, A. M., Hamilton, N., Hubbard, P. S., Pugh, M., & Ibrahim, M. (2005) · Journal of Anatomy · doi:10.1111/j.1469-7580.2005.00458.x · Cited by 201 · see citing works
Alonso, G. (2004) · Glia · doi:10.1002/glia.20121 · Cited by 178 · see citing works
Pyramidal Neurons Are Generated from Oligodendroglial Progenitor Cells in Adult Piriform Cortex
Guo, F., Maeda, Y., Ma, J., Xu, J., Horiuchi, M., Miers, L. A., Vaccarino, F. M., & Pleasure, D. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1360-10.2010 · Cited by 176 · see citing works
Early Postnatal Proteolipid Promoter-Expressing Progenitors Produce Multilineage CellsIn Vivo
Guo, F., Ma, J., McCauley, E., Bannerman, P. G. C., & Pleasure, D. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5653-08.2009 · Cited by 131 · see citing works
Sellers, D. L., Maris, D. O., & Horner, P. J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4538-08.2009 · Cited by 130 · see citing works
Ermin, A Myelinating Oligodendrocyte-Specific Protein That Regulates Cell Morphology
Brockschnieder, D., Sabanay, H., Riethmacher, D., & Peles, E. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4317-05.2006 · Cited by 128 · 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
Age-related myelin dynamics revealed by increased oligodendrogenesis and short internodes
Lasiene, J., Matsui, A., Sawa, Y., Wong, F., & Horner, P. J. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00462.x · Cited by 111 · see citing works
Acute treatment with tamoxifen reduces ischemic damage following middle cerebral artery occlusion
Kimelberg, H. K., Feustel, P. J., Jin, Y., Paquette, J., Boulos, A., Keller, R. W., & Tranmer, B. I. (2000) · NeuroReport · doi:10.1097/00001756-200008210-00014 · Cited by 108 · see citing works
Tamura, Y., Kataoka, Y., Cui, Y., Takamori, Y., Watanabe, Y., & Yamada, H. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05617.x · Cited by 104 · see citing works
Tian, D., Liu, J., Xie, M., Zhan, Y., Qu, W., Yu, Z., Tang, Z., Pan, D., & Wang, W. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06077.x · Cited by 98 · see citing works
An Fgfr3‐iCreERT2 transgenic mouse line for studies of neural stem cells and astrocytes
Young, K. M., Mitsumori, T., Pringle, N. P., Grist, M., Kessaris, N., & Richardson, W. D. (2010) · Glia · doi:10.1002/glia.20976 · Cited by 98 · see citing works
Self-citationNeurogenesis in the chronic lesions of multiple sclerosis
Chang, A., Smith, M. C., Yin, X., Fox, R., Staugaitis, S., & Trapp, B. (2007) · Brain : a journal of neurology · doi:10.1093/brain/awn157 · Cited by 90 · see citing works
Magnus, T., Coksaygan, T., Korn, T., Xue, H., Arumugam, T., Mughal, M. R., Eckley, D., Tang, S.-C., Detolla, L., Rao, M. S., et al. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21368 · Cited by 87 · see citing works
Zhao, J.-W., Raha-Chowdhury, R., Fawcett, J., & Watts, C. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06736.x · Cited by 84 · see citing works
Zhang, Y., Milatović, D., Aschner, M., Feustel, P. J., & Kimelberg, H. K. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.01.015 · Cited by 83 · see citing works
Neuroprotective activity of tamoxifen in permanent focal ischemia
Kimelberg, H. K., Jin, Y., Charniga, C. J., & Feustel, P. J. (2003) · Journal of neurosurgery · doi:10.3171/jns.2003.99.1.0138 · Cited by 83 · see citing works
Characterization of cells with proliferative activity after a brain injury
Tatsumi, K., Haga, S., Matsuyoshi, H., Inoue, M., Manabe, T., Makinodan, M., & Wanaka, A. (2005) · Neurochemistry International · doi:10.1016/j.neuint.2004.12.007 · Cited by 70 · see citing works
Golan, N., Adamsky, K., Kartvelishvily, E., Brockschnieder, D., Möbius, W., Spiegel, I., Roth, A. D., Thomson, C. E., Rechavi, G., & Peles, E. (2008) · Glia · doi:10.1002/glia.20688 · Cited by 59 · see citing works
Winkler, M. K., & Benveniste, E. N. (1998) · Glia · doi:10.1002/(sici)1098-1136(199802)22:2 · Cited by 50 · see citing works
A novel family of ancient vertebrate odorant receptors
Berghard, A., & Dryer, L. (1998) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(19981115)37:3 · Cited by 50 · see citing works
Butt, A. M., Hornby, M. F., Ibrahim, M., Kirvell, S. L., Graham, A., & Berry, M. (1997) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1996.0590 · Cited by 46 · see citing works
Zhang, B., Cao, Q., Guo, A., Chu, H., Chan, Y. G., Buschdorf, J. P., Low, B. C., Ling, E., & Liang, F. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500952102 · Cited by 41 · see citing works
NG2 cells differentiate into astrocytes in cerebellar slices
Leoni, G., Rattray, M., & Butt, A. M. (2009) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2009.07.007 · Cited by 35 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Oligodendrocyte Dynamics in the Healthy Adult CNS: Evidence for Myelin Remodeling
Young, K. M., Psachoulia, K., Tripathi, R. B., Dunn, S.-J., Cossell, L., Attwell, D., Tohyama, K., & Richardson, W. D. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.006 · Cited by 872 · see citing works
“A short time later (P120+7), 19.9% ± 3.2% of all optic nerve OPs (defined by NG2 immunolabeling) were YFP labeled (mean ±SD, n = 3 mice), less than in the adult corpus callosum ( 45%; Rivers et al., 2008) or spinal cord ( 39%; Zawadzka et al., 2010; Tripathi et al., 2010).”
BackgroundInfluentialSelf-citationHughes, E. G., Kang, S. H., Fukaya, M., & Bergles, D. E. (2013) · Nature Neuroscience · doi:10.1038/nn.3390 · Cited by 808 · 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
Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis
Falcão, A. M., van Bruggen, D., Marques, S., Meijer, M., Jäkel, S., Agirre, E., Samudyata, Floriddia, E. M., Vanichkina, D. P., ffrench-Constant, C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0236-y · Cited by 579 · 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
NG2-glia as multipotent neural stem cells: fact or fantasy?
Richardson, W. D., Young, K. M., Tripathi, R. B., & McKenzie, I. (2011) · Neuron · doi:10.1016/j.neuron.2011.05.013 · Cited by 300 · see citing works
Self-citationDe Biase, L. M., Kang, S. H., Baxi, E. G., Fukaya, M., Pucak, M. L., Mishina, M., Calabresi, P. A., & Bergles, D. E. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2455-11.2011 · Cited by 161 · see citing works
Neuronal APOE4 removal protects against tau-mediated gliosis, neurodegeneration and myelin deficits
Koutsodendris, N., Blumenfeld, J., Agrawal, A., Traglia, M., Grone, B., Zilberter, M., Yip, O., Rao, A., Nelson, M. R., Hao, Y., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00368-3 · Cited by 132 · see citing works
Bribián, A., Fontana, X., Llorens, F., Gavín, R., Reina, M., García-Verdugo, J. M., Torres, J. M., de Castro, F., & Río, J. A. D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033872 · Cited by 70 · see citing works
Butti, E., Bacigaluppi, M., Chaabane, L., Ruffini, F., Brambilla, E., Berera, G., Montonati, C., Quattrini, A., & Martino, G. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.0227-18.2019 · Cited by 67 · see citing works
Yahn, S. L., Li, J., Goo, I., Gao, H., Brambilla, R., & Lee, J. K. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104674 · Cited by 45 · see citing works
Colón, J. M., Torrado, A. I., Cajigas, Á., Santiago, J. M., Salgado, I. K., Arroyo, Y., & Miranda, J. D. (2016) · Journal of Neurotrauma · doi:10.1089/neu.2015.4111 · Cited by 35 · see citing works
Khaw, Y. M., Tierney, A., Cunningham, C., Soto-Díaz, K., Kang, E., Steelman, A. J., & Inoue, M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2017213118 · Cited by 32 · see citing works
Pukos, N., & McTigue, D. M. (2020) · PLOS ONE · doi:10.1371/journal.pone.0235232 · Cited by 9 · see citing works
- Authors
- Tripathi, R. B., Rivers, L. E., Young, K. M., Jamen, F., & Richardson, W. D.
- Affiliations
- University College London (GB)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Richardson, William D.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-12-01
- Volume
- 30
- Issue
- 48
- Pages
- 16383-16390
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3063541
- OpenAlex
- W1979552960
- Cited by
- 277
- References
- 47
- Citations by year
- 2026: 12 · 2025: 5 · 2024: 16 · 2023: 19 · 2022: 11 · 2021: 13 · 2020: 31 · 2019: 23 · 2018: 18 · 2017: 15 · 2016: 19 · 2015: 15 · 2014: 23 · 2013: 23 · 2012: 23
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Wellcome Trust (080513, 86419)
- Alzheimer's Society
- University College London
- European Commission
- Eisai
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- oligodendrocyte precursor cells, PDGFRA, oligodendrocyte differentiation, astrocyte differentiation, demyelination, experimental autoimmune encephalomyelitis, multiple sclerosis, myelination, reactive astrocytes, spinal cord
- MeSH terms
- Chondroitin Sulfate Proteoglycan 4, Animals, Antigens, Astrocytes, Demyelinating Diseases, Encephalomyelitis, Autoimmune, Experimental, Female, Male, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Transgenic, Neuroglia, Oligodendroglia, Proteoglycans, Mice, Neurogenesis
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
