Epigenetic regulation of neural cell differentiation plasticity in the adult mammalian brain

Jun Kohyama, Takuro Kojima, Eriko Takatsuka, Toru Yamashita, Jun Namiki, Jenny Hsieh, Fred H. Gage, Masakazu Namihira, Hideyuki Okano, Kazunobu Sawamoto, Kinichi Nakashima

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Neural stem/progenitor cells (NSCs/NPCs) give rise to neurons, astrocytes, and oligodendrocytes. It has become apparent that intracellular epigenetic modification including DNA methylation, in concert with extracellular cues such as cytokine signaling, is deeply involved in fate specification of NSCs/NPCs by defining cell-type specific gene expression. However, it is still unclear how differentiated neural cells retain their specific attributes by repressing cellular properties characteristic of other lineages. In previous work we have shown that methyl-CpG binding protein transcriptional repressors (MBDs), which are expressed predominantly in neurons in the central nervous system, inhibit astrocyte-specific gene expression by binding to highly methylated regions of their target genes. Here we report that oligodendrocytes, which do not express MBDs, can transdifferentiate into astrocytes both in vitro (cytokine stimulation) and in vivo (ischemic injury) through the activation of the JAK/STAT signaling pathway. These findings suggest that differentiation plasticity in neural cells is regulated by cell-intrinsic epigenetic mechanisms in collaboration with ambient cell-extrinsic cues.

Original languageEnglish
Pages (from-to)18012-18017
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number46
DOIs
Publication statusPublished - Nov 18 2008
Externally publishedYes

Keywords

  • Glia
  • JAK/STAT

ASJC Scopus subject areas

  • General

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    Kohyama, J., Kojima, T., Takatsuka, E., Yamashita, T., Namiki, J., Hsieh, J., Gage, F. H., Namihira, M., Okano, H., Sawamoto, K., & Nakashima, K. (2008). Epigenetic regulation of neural cell differentiation plasticity in the adult mammalian brain. Proceedings of the National Academy of Sciences of the United States of America, 105(46), 18012-18017. https://doi.org/10.1073/pnas.0808417105