Coordinated regulation of cortical astrocyte maturation by OLIG1 and OLIG2 through BMP7 signaling modulation

Ziwu Wang; Yu Tian; Tongye Fu; Feihong Yang; Jialin Li; Lin Yang; Wen Zhang; Wenhui Zheng; Xin Jiang; Zhejun Xu; Yan You; Xiaosu Li; Guoping Liu; Yunli Xie; Zhengang Yang; Dashi Qi; Zhuangzhi Zhang

doi:10.1016/j.jgg.2025.03.008

文章导航 > Journal of Genetics and Genomics > 2025 > 优先出版

Ziwu Wang, Yu Tian, Tongye Fu, Feihong Yang, Jialin Li, Lin Yang, Wen Zhang, Wenhui Zheng, Xin Jiang, Zhejun Xu, Yan You, Xiaosu Li, Guoping Liu, Yunli Xie, Zhengang Yang, Dashi Qi, Zhuangzhi Zhang. Coordinated regulation of cortical astrocyte maturation by OLIG1 and OLIG2 through BMP7 signaling modulation[J]. 遗传学报. doi: 10.1016/j.jgg.2025.03.008

引用本文:

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引用本文:

Citation:

Coordinated regulation of cortical astrocyte maturation by OLIG1 and OLIG2 through BMP7 signaling modulation

doi: 10.1016/j.jgg.2025.03.008

a. Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200030, China;
b. Department of Anesthesiology, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
c. Neurovascular Center, Changhai Hospital, Institute of Neuroscience, MOE Key Laboratory of Molecular Neurobiology, NMU, Shanghai 200433, China;
d. Center for Clinical Research and Translational Medicine, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200000, China

基金项目:

This study was supported by the National Natural Science Foundation of China (NSFC 82271197, 81974175, 31820103006, 32070971, 32200792, and 32200776).

详细信息

通讯作者:
Dashi Qi,E-mail:qidashi@fudan.edu.cn

Zhuangzhi Zhang,E-mail:zz_zhang@fudan.edu.cn

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出版历程
- 收稿日期: 2024-12-18
- 录用日期: 2025-03-17
- 修回日期: 2025-03-17
- 网络出版日期: 2025-07-11

Coordinated regulation of cortical astrocyte maturation by OLIG1 and OLIG2 through BMP7 signaling modulation

a. Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200030, China;
b. Department of Anesthesiology, Shuguang Hospital Affiliated with Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
c. Neurovascular Center, Changhai Hospital, Institute of Neuroscience, MOE Key Laboratory of Molecular Neurobiology, NMU, Shanghai 200433, China;
d. Center for Clinical Research and Translational Medicine, Yangpu Hospital, School of Medicine, Tongji University, Shanghai 200000, China

Funds:

This study was supported by the National Natural Science Foundation of China (NSFC 82271197, 81974175, 31820103006, 32070971, 32200792, and 32200776).

摘要

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.
- Astrocyte /
- Bmp7 /
- Olig1/2 /
- Transcription factor /
- Cortex
Abstract:
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.
- Astrocyte /
- Bmp7 /
- Olig1/2 /
- Transcription factor /
- Cortex

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Coordinated regulation of cortical astrocyte maturation by OLIG1 and OLIG2 through BMP7 signaling modulation

doi: 10.1016/j.jgg.2025.03.008

通讯作者:
Dashi Qi,E-mail:qidashi@fudan.edu.cn

Zhuangzhi Zhang,E-mail:zz_zhang@fudan.edu.cn

计量

Coordinated regulation of cortical astrocyte maturation by OLIG1 and OLIG2 through BMP7 signaling modulation

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留言板

Coordinated regulation of cortical astrocyte maturation by OLIG1 and OLIG2 through BMP7 signaling modulation

doi: 10.1016/j.jgg.2025.03.008

通讯作者: Dashi Qi,E-mail:qidashi@fudan.edu.cn Zhuangzhi Zhang,E-mail:zz_zhang@fudan.edu.cn

计量

出版历程

Coordinated regulation of cortical astrocyte maturation by OLIG1 and OLIG2 through BMP7 signaling modulation

计量

出版历程

目录

通讯作者:
Dashi Qi,E-mail:qidashi@fudan.edu.cn

Zhuangzhi Zhang,E-mail:zz_zhang@fudan.edu.cn