Abstract
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 language | English |
|---|---|
| Pages (from-to) | 2744-2752 |
| Number of pages | 9 |
| Journal | STEM CELLS |
| Volume | 27 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 1 2009 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Cell Biology
- Developmental Biology
- Molecular Medicine
Cite this
Astrocyte differentiation of neural precursor cells is enhanced by retinoic acid through a change in epigenetic modification. / Asano, Hirotsugu; Aonuma, Makoto; Sanosaka, Tsukasa; Kohyama, Jun; Namihira, Masakazu; Nakashima, Kinichi.
In: STEM CELLS, Vol. 27, No. 11, 01.11.2009, p. 2744-2752.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Astrocyte differentiation of neural precursor cells is enhanced by retinoic acid through a change in epigenetic modification
AU - Asano, Hirotsugu
AU - Aonuma, Makoto
AU - Sanosaka, Tsukasa
AU - Kohyama, Jun
AU - Namihira, Masakazu
AU - Nakashima, Kinichi
PY - 2009/11/1
Y1 - 2009/11/1
N2 - 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.
AB - 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.
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U2 - 10.1002/stem.176
DO - 10.1002/stem.176
M3 - Article
C2 - 19609931
AN - SCOPUS:72849129005
VL - 27
SP - 2744
EP - 2752
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 11
ER -