Astrocyte differentiation of neural precursor cells is enhanced by retinoic acid through a change in epigenetic modification

Hirotsugu Asano, Makoto Aonuma, Tsukasa Sanosaka, Jun Kohyama, Masakazu Namihira, Kinichi Nakashima

研究成果: Article査読

86 被引用数 (Scopus)

抄録

Neurons, astrocytes, and oligodendrocytes - the three major cell types that comprise the central nervous system - are generated from common multipotent neural precursor cells (NPCs). Members of the interleukin-6 family of cytokines, including leukemia inhibitory factor (LIF), induce astrocyte differentiation of NPCs by activating the transcription factor signal transducer and activator of transcription 3 (STAT3). We show here that retinoic acid (RA) facilitates LIFinduced astrocyte differentiation of NPCs. RA and LIF synergistically activate the promoter of gfap, which encodes the astrocytic marker glial fibrillary acidic protein, and a putative RA response element in the promoter was found to be critical for this activation. Histone H3 acetylation around the STAT-binding site in the gfap promoter was increased in NPCs treated with RA, allowing STAT3 to gain access to the promoter more efficiently. These results suggest that RA acts in concert with LIF to induce astrocyte differentiation of NPCs through an epigenetic mechanism that involves cross-talk between distinct signaling pathways.

本文言語English
ページ(範囲)2744-2752
ページ数9
ジャーナルStem Cells
27
11
DOI
出版ステータスPublished - 2009 11月
外部発表はい

ASJC Scopus subject areas

  • 分子医療
  • 発生生物学
  • 細胞生物学

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