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 new 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. ScRNA-seq were performed on FACS sorted tdT+ cells from the P1 Olig2f/f;IS-reporter mice cortex which were electroporated of pCAG-Cre plasmid at E15.The cortex were immediately submerged in fresh ice-cold Hanks balanced salt solution and was then cut into pieces and dissociated into a single-cell suspension using a Papain Cell Dissociation Kit according to the manufacturer’s instructions.