Yin Yang 1 Specifically Supports the Development of Olig2 Positive Cerebellar Astrocytes

Astrocytes regulate the assembly and functions of neural circuits, contribute to synaptic homeostasis, provide metabolic support to neurons, and control ion balance and blood-brain barrier integrity. These cells are morphologically and molecularly very heterogeneous and perform unique functions to accommodate the needs of subsets of neurons. In this study, we identified and characterized a subpopulation of cerebellar astrocytes expressing the transcription factor Olig2 (O2AST). We defined their molecular identity and transcriptional divergence from other well-established subpopulations of cerebellar astrocytes and cells of the oligodendrocyte lineage that also express Olig2. Specific deletion of Olig2 from astrocytes in vivo affects the locomotion of mice. We found that cerebellar O2AST are relatively abundant in the cerebellar nuclei but not in the cerebellar lobes. Cerebellar O2AST highly express a set of unique genes, including Slc6a11, Gpc5, Igsf1, Alpl, and Egfl6. Furthermore, we examined the regulatory influence of the transcription factor Yin Yang 1 (YY1), known to control maturation of cerebellar astrocytes, on O2AST differentiation and morphology. Specific deletion of Yy1 from astrocytes increases the number of O2AST in the cerebellar nuclei, affects O2AST differentiation, and cross-communication with the cells of oligodendrocyte lineage, diminishing differentiation of oligodendrocyte precursor cells (OPCs) to mature oligodendrocytes. In sum, our findings reveal a distinct, transcriptionally unique subpopulation of astrocytes expressing Olig2 in the cerebellum, uncovering novel regulatory mechanisms orchestrated by Yy1 during postnatal development.