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

Research output: Contribution to journalArticle

72 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2744-2752
Number of pages9
JournalStem Cells
Issue number11
Publication statusPublished - 2009 Nov
Externally publishedYes



  • Astrocyte
  • Histone acetylation
  • Neural precursor cells
  • Retinoic acid
  • STAT3

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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