Coordinated regulation of cortical astrocyte maturation by OLIG1 and OLIG2 through BMP7 signaling modulation
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.
Authors
- Jialin Li (ORCID: https://orcid.org/0009-0002-9994-728X)
- Zhejun Xu (ORCID: https://orcid.org/0000-0002-1933-6300)
- Zhengang Yang (ORCID: https://orcid.org/0000-0003-2447-6540)
- Zi‐Wu Wang
- Wenhui Zheng (ORCID: https://orcid.org/0000-0003-1426-2135)
- Zhuangzhi Zhang (ORCID: https://orcid.org/0000-0002-9860-6689)
- Xiaosu Li (ORCID: https://orcid.org/0009-0004-3034-1348)
- Lin Yang (ORCID: https://orcid.org/0000-0003-2193-9597)
- Tao Fu (ORCID: https://orcid.org/0000-0003-1783-2631)
- Feihong Yang
- Guoping Liu (ORCID: https://orcid.org/0000-0002-2352-1138)
- Wen Zhang (ORCID: https://orcid.org/0000-0001-7808-9867)
- Xin Jiang (ORCID: https://orcid.org/0000-0002-5662-2322)
- Yan You (ORCID: https://orcid.org/0009-0009-7917-0590)
- Dashi Qi (ORCID: https://orcid.org/0000-0002-0614-7068)
- Yuliang Xie (ORCID: https://orcid.org/0000-0001-6084-7113)
- Yu Tian (ORCID: https://orcid.org/0000-0001-5465-0023)
Institutions
- Second Military Medical University (CN)
- Fudan University (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Changhai Hospital (CN)
- Institute of Neurobiology and Molecular Medicine (IT)
- Obstetrics and Gynecology Hospital of Fudan University (CN)
- Shuguang Hospital (CN)
- Children's Hospital of Fudan University (CN)
Publication Details
- Journal
- Journal of genetics and genomics/Journal of Genetics and Genomics
- Published
- 2025-03-25
- DOI
- https://doi.org/10.1016/j.jgg.2025.03.008
- Citations
- 4
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 3.37
Funders
- National Natural Science Foundation of China