复旦大学张壮志研究团队近日取得一项新成果。经过不懈努力，他们揭示了通过BMP7信号调节，OLIG1和OLIG2协调调节皮质星形胶质细胞成熟。相关论文发表在2025年3月24日出版的《遗传学报》杂志上。

在这项研究中，该研究组发现bHLH转录因子OLIG1和OLIG2是皮质星形胶质细胞成熟的重要协调者。课题组人员证明OLIG1和OLIG2通过调节Bmp7的表达协同调节皮质星形胶质细胞成熟。基因消融OLIG1和OLIG2导致星形胶质细胞形态缺陷，包括过程复杂性降低和基因表达谱不成熟。单细胞RNA测序揭示了向不太成熟的星形胶质细胞状态的转变，其特征是HOPX和GFAP水平升高，类似于人类星形胶质细胞。从机制上讲，OLIG1和OLIG2直接与Bmp7增强子结合，抑制其表达，促进星形胶质细胞成熟。体内Bmp7的过表达复制了OLIG1/2双突变体中的星形细胞缺陷，证实了Bmp7信号在这一过程中的关键作用。这些发现提供了调控星形胶质细胞发育的转录和信号通路的见解，并强调了OLIG1和OLIG2是皮质星形胶质细胞成熟的关键调节因子，对理解神经系统疾病中的胶质功能障碍具有潜在的意义。

研究人员表示，星形胶质细胞成熟对大脑功能至关重要，但调控这一过程的机制尚不清楚。

附：英文原文

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

Author: Dashi Qi d, Zhuangzhi Zhang a

Issue&Volume: 2025/03/24

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.

DOI: 10.1016/j.jgg.2025.03.008

Source: https://www.sciencedirect.com/science/article/pii/S1673852725000815