[Hypoxia epigenetically bestows astrocytic differentiation potential on human pluripotent cell-derived neural stem/precursor cells]

Nihon Yakurigaku Zasshi. 2019;153(2):54-60. doi: 10.1254/fpj.153.54.
[Article in Japanese]

Abstract

The central nervous system (CNS) is composed of three major cell types, neurons, astrocytes, and oligodendrocytes, which differentiate from common multipotent neural stem/precursor cells (NS/PCs). However, NS/PCs do not have this multipotentiality from the beginning: neurons are generated first and astrocytes are later during CNS development. This developmental progression is observed in vitro by using human (h) NS/PCs derived from pluripotent cells, such as embryonic- and induced pluripotent-stem cells (ES/iPSCs), however, in contrast to rodent's pluripotent cells, they require quite long time to obtain astrocytic differentiation potential. Here, we show that hypoxia confers astrocytic differentiation potential on hNS/PCs through epigenetic alteration for gene regulation. Furthermore, we found that these molecular mechanisms can be applied to functional analysis of patient' iPSC-derived astrocytes. In this review, we summarize recent findings that address molecular mechanisms of epigenetic and transcription factor-mediated regulation that specify NS/PC fate and the development of potential therapeutic strategies for treating astrocyte-mediated neurological disorders.

Publication types

  • Review

MeSH terms

  • Astrocytes / cytology*
  • Cell Differentiation
  • Cell Hypoxia
  • Cells, Cultured
  • Epigenesis, Genetic*
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Neural Stem Cells / cytology*
  • Neurogenesis