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Cited by 650Neurogenesis and neuroplasticity mechanismsMultiple Sclerosis Research StudiesMesenchymal stem cell research

CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination

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Zawadzka, Malgorzata, Rivers, Leanne E., Fancy, Stephen P.J., Zhao, Chao, Tripathi, Richa, Jamen, Françoise, Young, Kaylene, Goncharevich, Alexander +7 more·2010·Cell stem cell
DOI 10.1016/j.stem.2010.04.002PMC PMC3856868
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Abstract

After central nervous system (CNS) demyelination-such as occurs during multiple sclerosis-there is often spontaneous regeneration of myelin sheaths, mainly by oligodendrocytes but also by Schwann cells. The origins of the remyelinating cells have not previously been established. We have used Cre-lox fate mapping in transgenic mice to show that PDGFRA/NG2-expressing glia, a distributed population of stem/progenitor cells in the adult CNS, produce the remyelinating oligodendrocytes and almost all of the Schwann cells in chemically induced demyelinated lesions. In contrast, the great majority of reactive astrocytes in the vicinity of the lesions are derived from preexisting FGFR3-expressing cells, likely to be astrocytes. These data resolve a long-running debate about the origins of the main players in CNS remyelination and reveal a surprising capacity of CNS precursors to generate Schwann cells, which normally develop from the embryonic neural crest and are restricted to the peripheral nervous system.

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Crossref · 10.1016/j.stem.2010.04.002

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  • 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 Zawadzka et al., 2010

    The Results section, “Efficient Labeling of PDGFRA-Expressing Cells after Lysolecithin-Induced Demyelination” (page unavailable), reports approximately 39% YFP labeling in spinal cord precursor cells. That figure is the fraction of PDGFRA-positive cells in a demyelinated lesion, not a measurement of NG2-defined OPs in unlesioned adult spinal cord. This citation does not support the optic-nerve or corpus-callosum figures, which the sentence attributes elsewhere. (LLM, conf=0.86)

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  • The 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 [82]

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Authors
Zawadzka, M., Rivers, L. E., Fancy, S. P. J., Zhao, C., Tripathi, R., Jamen, F., Young, K., Goncharevich, A., Pohl, H., Rizzi, M., Rowitch, D. H., Kessaris, N., Suter, U., Richardson, W. D., & Franklin, R. J. M.
Affiliations
  • University College London (GB)
  • Howard Hughes Medical Institute (US)
  • University of Cambridge (GB)
  • ETH Zurich (CH)
Corresponding author
  • Richardson, William D.
  • Franklin, Robin J.M.
ORCID
Venue
Cell stem cell
Publisher
Elsevier BV
Published
2010-06
Volume
6
Issue
6
Pages
578-590
ISSN
  • 1875-9777 (ISSN-L)
  • 1934-5909
DOI
10.1016/j.stem.2010.04.002
PMC
PMC3856868
OpenAlex
W2152131288
Cited by
650
References
61
Citations by year
2026: 25 · 2025: 25 · 2024: 35 · 2023: 40 · 2022: 38 · 2021: 39 · 2020: 56 · 2019: 53 · 2018: 49 · 2017: 56 · 2016: 34 · 2015: 35 · 2014: 49 · 2013: 46 · 2012: 33
FWCI
11.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell stem cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eCite Digital Repository (University of Tasmania) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • Wellcome Trust (080513)
  • 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
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
central nervous system demyelination, remyelination, oligodendrocyte precursor cells, Schwann cells, glial progenitor cells, reactive astrocytes, multiple sclerosis, cell of origin, fate mapping
MeSH terms
Oligodendrocyte Transcription Factor 2, Animals, Astrocytes, Cells, Cultured, Central Nervous System, Demyelinating Diseases, Disease Models, Animal, Female, Lysophosphatidylcholines, Mice, Transgenic, Microscopy, Multiple Sclerosis, Nerve Regeneration, Nerve Tissue Proteins, Oligodendroglia, Schwann Cells, Integrases, Receptor, Platelet-Derived Growth Factor alpha, Mice, Receptor, Fibroblast Growth Factor, Type 3, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors, Adult Stem Cells

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