Notch1和Notch3指导性地将碱性成纤维细胞生长因子（bFGF）反应性多能神经祖细胞限制为星形胶质细胞命运。

Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate.

作者信息

Tanigaki K, Nogaki F, Takahashi J, Tashiro K, Kurooka H, Honjo T

机构信息

Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe Sakyo, 606-8501, Kyoto, Japan.

出版信息

Neuron. 2001 Jan;29(1):45-55. doi: 10.1016/s0896-6273(01)00179-9.

DOI:10.1016/s0896-6273(01)00179-9

PMID:11182080

Abstract

Notch1 has been shown to induce glia in the peripheral nervous system. However, it has not been known whether Notch can direct commitment to glia from multipotent progenitors of the central nervous system. Here we present evidence that activated Notch1 and Notch3 promotes the differentiation of astroglia from the rat adult hippocampus-derived multipotent progenitors (AHPs). Quantitative clonal analysis indicates that the action of Notch is likely to be instructive. Transient activation of Notch can direct commitment of AHPs irreversibly to astroglia. Astroglial induction by Notch signaling was shown to be independent of STAT3, which is a key regulatory transcriptional factor when ciliary neurotrophic factor (CNTF) induces astroglia. These data suggest that Notch provides a CNTF-independent instructive signal of astroglia differentiation in CNS multipotent progenitor cells.

摘要

Notch1已被证明可在外周神经系统中诱导神经胶质细胞生成。然而，目前尚不清楚Notch是否能引导中枢神经系统的多能祖细胞定向分化为神经胶质细胞。在此，我们提供证据表明，激活的Notch1和Notch3可促进大鼠成年海马来源的多能祖细胞（AHPs）向星形胶质细胞分化。定量克隆分析表明，Notch的作用可能具有指导意义。Notch的短暂激活可使AHPs不可逆地定向分化为星形胶质细胞。Notch信号介导的星形胶质细胞诱导被证明独立于STAT3，而STAT3是睫状神经营养因子（CNTF）诱导星形胶质细胞时的关键调控转录因子。这些数据表明，Notch在中枢神经系统多能祖细胞中提供了一种独立于CNTF的星形胶质细胞分化指导信号。