MEIS1 is Required for Establishing Bergmann Glia-Specific Properties in the Developing Cerebellum

Abstract

Compared to normal multipolar astrocytes, Bergmann glial cells (BGs), specifically differentiated astrocytes in the cerebellum, possess unique unipolar morphology and additional cellular functions. However, the molecular mechanisms that confer BG-specific properties onto normal multipolar astrocytes remain unknown. Here, we show that the transcription factor, MEIS1, is involved in BGs acquiring their unique characteristics. Targeted disruption of Meis1 in the whole cerebellum or astroglial lineage cells resulted in a marked reduction of BGs accompanied by an increase in multipolar astrocytes in mice. Postnatal deletion of Meis1 in Bergmann glia-like progenitors (BGLPs), which produce both BGs and multipolar astrocytes, suppressed their differentiation into BGs while promoting into multipolar astrocytes. Single-cell RNA sequencing, immunohistochemistry, and ChIP-Atlas analyses indicated that MEIS1 directly upregulates expression of BG-specific genes, including Vimentin and Zeb2, which are known to contribute to the correct localization and the unipolar process formation of BGs. These findings suggest that MEIS1 promotes the endowment of BG-specific properties to astrocytes by controlling the expression of BG-specific genes, thereby ensuring proper differentiation of BGLPs into BGs.