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

Tetsuro Yasui, Kinichi Nakashima

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)54-60
Number of pages7
JournalFolia Pharmacologica Japonica
Volume153
Issue number2
DOIs
Publication statusPublished - Jan 1 2019

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Neural Stem Cells
Astrocytes
Epigenomics
Central Nervous System
Multipotent Stem Cells
Neurons
Induced Pluripotent Stem Cells
Oligodendroglia
Nervous System Diseases
Rodentia
Transcription Factors
Hypoxia
Genes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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