奥利格2
星形胶质细胞
细胞生物学
神经科学
骨形态发生蛋白7
调制(音乐)
化学
生物
骨形态发生蛋白
少突胶质细胞
基因
生物化学
物理
中枢神经系统
髓鞘
声学
作者
Zi‐Wu Wang,Yu Tian,Tao Fu,Feihong Yang,Jialin Li,Lin Yang,Wen Zhang,Wenhui Zheng,Xin Jiang,Zhejun Xu,Yan You,Xiaosu Li,Guoping Liu,Yuliang Xie,Zhengang Yang,Dashi Qi,Zhuangzhi Zhang
标识
DOI:10.1016/j.jgg.2025.03.008
摘要
Astrocyte maturation is crucial for brain function, yet the mechanisms regulating this process remain poorly understood. In this study, we identify the bHLH transcription factors Olig1 and Olig2 as essential coordinators of cortical astrocyte maturation. We demonstrate that Olig1 and Olig2 work synergistically to regulate cortical astrocyte maturation by modulating Bmp7 expression. Genetic ablation of both Olig1 and Olig2 results in defective astrocyte morphology, including reduced process complexity and an immature gene expression profile. Single-cell RNA sequencing reveals a shift towards a less mature astrocyte state, marked by elevated levels of HOPX and GFAP, resembling human astrocytes. Mechanistically, Olig1 and Olig2 bind directly to the Bmp7 enhancer, repressing its expression to promote astrocyte maturation. Overexpression of Bmp7 in vivo replicates the astrocyte defects seen in Olig1/2 double mutants, confirming the critical role of BMP7 signaling in this process. These findings provide insights into the transcriptional and signaling pathways regulating astrocyte development and highlight Olig1 and Olig2 as key regulators of cortical astrocyte maturation, with potential implications for understanding glial dysfunction in neurological diseases.
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