抄録
Human neural precursor cells (hNPCs) derived from pluripotent stem cells display a high propensity for neuronal differentiation, but they require long-term culturing to differentiate efficiently into astrocytes. The mechanisms underlying this biased fate specification of hNPCs remain elusive. Here, we show that hypoxia confers astrocytic differentiation potential on hNPCs through epigenetic gene regulation, and that this was achieved by cooperation between hypoxia-inducible factor 1α and Notch signaling, accompanied by a reduction of DNA methylation level in the promoter region of a typical astrocyte-specific gene, Glial fibrillary acidic protein. Furthermore, we found that this hypoxic culture condition could be applied to rapid generation of astrocytes from Rett syndrome patient-derived hNPCs, and that these astrocytes impaired neuronal development. Thus, our findings shed further light on the molecular mechanisms regulating hNPC differentiation and provide attractive tools for the development of therapeutic strategies for treating astrocyte-mediated neurological disorders.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 1743-1756 |
| ページ数 | 14 |
| ジャーナル | Stem Cell Reports |
| 巻 | 8 |
| 発行部数 | 6 |
| DOI | |
| 出版物ステータス | 出版済み - 6 6 2017 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Genetics
- Developmental Biology
- Cell Biology
これを引用
Hypoxia Epigenetically Confers Astrocytic Differentiation Potential on Human Pluripotent Cell-Derived Neural Precursor Cells. / Yasui, Tetsuro; Uezono, Naohiro; Nakashima, Hideyuki; Noguchi, Hirofumi; Matsuda, Taito; Noda-Andoh, Tomoko; Okano, Hideyuki; Nakashima, Kinichi.
：: Stem Cell Reports, 巻 8, 番号 6, 06.06.2017, p. 1743-1756.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - Hypoxia Epigenetically Confers Astrocytic Differentiation Potential on Human Pluripotent Cell-Derived Neural Precursor Cells
AU - Yasui, Tetsuro
AU - Uezono, Naohiro
AU - Nakashima, Hideyuki
AU - Noguchi, Hirofumi
AU - Matsuda, Taito
AU - Noda-Andoh, Tomoko
AU - Okano, Hideyuki
AU - Nakashima, Kinichi
PY - 2017/6/6
Y1 - 2017/6/6
N2 - Human neural precursor cells (hNPCs) derived from pluripotent stem cells display a high propensity for neuronal differentiation, but they require long-term culturing to differentiate efficiently into astrocytes. The mechanisms underlying this biased fate specification of hNPCs remain elusive. Here, we show that hypoxia confers astrocytic differentiation potential on hNPCs through epigenetic gene regulation, and that this was achieved by cooperation between hypoxia-inducible factor 1α and Notch signaling, accompanied by a reduction of DNA methylation level in the promoter region of a typical astrocyte-specific gene, Glial fibrillary acidic protein. Furthermore, we found that this hypoxic culture condition could be applied to rapid generation of astrocytes from Rett syndrome patient-derived hNPCs, and that these astrocytes impaired neuronal development. Thus, our findings shed further light on the molecular mechanisms regulating hNPC differentiation and provide attractive tools for the development of therapeutic strategies for treating astrocyte-mediated neurological disorders.
AB - Human neural precursor cells (hNPCs) derived from pluripotent stem cells display a high propensity for neuronal differentiation, but they require long-term culturing to differentiate efficiently into astrocytes. The mechanisms underlying this biased fate specification of hNPCs remain elusive. Here, we show that hypoxia confers astrocytic differentiation potential on hNPCs through epigenetic gene regulation, and that this was achieved by cooperation between hypoxia-inducible factor 1α and Notch signaling, accompanied by a reduction of DNA methylation level in the promoter region of a typical astrocyte-specific gene, Glial fibrillary acidic protein. Furthermore, we found that this hypoxic culture condition could be applied to rapid generation of astrocytes from Rett syndrome patient-derived hNPCs, and that these astrocytes impaired neuronal development. Thus, our findings shed further light on the molecular mechanisms regulating hNPC differentiation and provide attractive tools for the development of therapeutic strategies for treating astrocyte-mediated neurological disorders.
UR - http://www.scopus.com/inward/record.url?scp=85020315491&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020315491&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2017.05.001
DO - 10.1016/j.stemcr.2017.05.001
M3 - Article
C2 - 28591654
AN - SCOPUS:85020315491
VL - 8
SP - 1743
EP - 1756
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 6
ER -