Loss of NFIX Transcription Factor Biases Postnatal Neural Stem/Progenitor Cells Toward Oligodendrogenesis

Stem Cells Dev. 2015 Sep 15;24(18):2114-26. doi: 10.1089/scd.2015.0136. Epub 2015 Jul 28.

Abstract

Murine postnatal neural stem cells (NSCs) give rise to neurons, astrocytes, or oligodendrocytes (OLs); however, our knowledge of the genes that control this lineage specification is incomplete. In this study, we show that nuclear factor I X (NFIX), a transcription factor known to regulate NSC quiescence, also suppresses oligodendrogenesis (ODG) from NSCs. Immunostaining reveals little or no expression of NFIX in OL lineage cells both in vivo and in vitro. Loss of NFIX from subventricular zone (SVZ) NSCs results in enhanced ODG both in vivo and in vitro, while forced expression of NFIX blocks NSC differentiation into OLs in vitro. RNA-seq analysis shows that genes previously shown to be differentially expressed in OL progenitors are significantly enriched in RNA from Nfix(-/-) versus wild-type NSCs. These data indicate that NFIX influences the lineage specification of postnatal SVZ NSCs, specifically suppressing ODG.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Cell Lineage
  • Cells, Cultured
  • Lateral Ventricles / cytology
  • Lateral Ventricles / embryology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NFI Transcription Factors / genetics*
  • Neural Stem Cells / cytology*
  • Neurogenesis / physiology*
  • Neurons / cytology
  • Oligodendroglia / cytology*
  • SOXE Transcription Factors / metabolism

Substances

  • NFI Transcription Factors
  • Nfix protein, mouse
  • SOXE Transcription Factors
  • Sox10 protein, mouse