Transient Redirection of SVZ Stem Cells to Oligodendrogenesis by FGFR3 Activation Promotes Remyelination

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Stimulating oligodendrocyte (OL) production from endogenous progenitor cells is an important strategy for myelin repair and functional restoration after disease or injury-induced demyelination. Subventricular zone (SVZ) stem cells are multipotential, generating neurons and oligodendroglia. The factors that regulate the fate of these stem cells are poorly defined. In this study, we show that genetically increasing fibroblast growth factor receptor-3 (FGFR3) activity in adult SVZ stem cells transiently and dramatically redirects their differentiation from the neuronal to the oligodendroglial lineage after pathological demyelination. The increased SVZ-derived oligodendrogenesis leads to improved OL regeneration and myelin repair, not only in the corpus callosum (a normal destination for SVZ-derived oligodendroglial cells), but also in the lower cortical layers. This study identifies FGF signaling as a potent target for improving endogenous SVZ-derived OL regeneration and remyelination. In this article, Hébert and colleagues show that adult neural stem cells can be made to switch the cell type they produce in vivo, from neurons to oligodendrocytes, by increasing levels of FGFR3 activity in the stem cells. The result of this increased oligodendrogenesis is a greater ability to remyelinate axons after acute or chronic lesions.

Original languageEnglish (US)
Pages (from-to)1223-1231
Number of pages9
JournalStem Cell Reports
Volume12
Issue number6
DOIs
StatePublished - Jun 11 2019

Keywords

  • FGF receptor activity
  • adult neural stem cells
  • cell fate reprogramming in vivo
  • oligodendrogenesis
  • remyelination
  • subventricular zone

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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