4.6 Article

Yin Yang 1 controls cerebellar astrocyte maturation

Journal

GLIA
Volume 71, Issue 10, Pages 2437-2455

Publisher

WILEY
DOI: 10.1002/glia.24434

Keywords

astrocytes; cerebellum; heterogeneity; maturation; YY1

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The transcription factor YY1 is expressed in astrocytes and plays a critical role in regulating gene expression and maturation of cerebellar astrocytes. It is also necessary for maintaining the mature phenotype of astrocytes in the adult cerebellum.
Diverse subpopulations of astrocytes tile different brain regions to accommodate local requirements of neurons and associated neuronal circuits. Nevertheless, molecular mechanisms governing astrocyte diversity remain mostly unknown. We explored the role of a zinc finger transcription factor Yin Yang 1 (YY1) that is expressed in astrocytes. We found that specific deletion of YY1 from astrocytes causes severe motor deficits in mice, induces Bergmann gliosis, and results in simultaneous loss of GFAP expression in velate and fibrous cerebellar astrocytes. Single cell RNA-seq analysis showed that YY1 exerts specific effects on gene expression in subpopulations of cerebellar astrocytes. We found that although YY1 is dispensable for the initial stages of astrocyte development, it regulates subtype-specific gene expression during astrocyte maturation. Moreover, YY1 is continuously needed to maintain mature astrocytes in the adult cerebellum. Our findings suggest that YY1 plays critical roles regulating cerebellar astrocyte maturation during development and maintaining a mature phenotype of astrocytes in the adult cerebellum.

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