# Regulation of astrocyte diversity in the cerebellum

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2021 · $460,270

## Abstract

Astrocytes are extremely diverse across different brain regions and perform specialized
function. Diversity of these cells is generated by initial patterning and then promoted by region-
specific communication with neurons to fine-tune astrocytes to the local requirements. While
important insights have been gained into the diversity of astrocytes using novel approaches,
molecular mechanisms controlling their diversity remain mostly elusive. In the cerebellum,
astrocytes differentiate into highly specialized Bergmann glia of the molecular layer, velate
astrocytes of the granular cell layer, and fibrous astrocytes of the white matter. This proposal aims
at understanding mechanisms that regulate diverse astrocyte subpopulations in the cerebellum.
Our results strongly suggest that a transcription factor, Yin Yang 1 (YY1), is essential for
sustaining the distinct functions of astrocyte subpopulations in both the developing and the adult
cerebellum. Deletion of YY1 in cerebellar astrocytes manifests in contrasting effects in the
molecular layer versus the granular cell layer and white matter by post-natal day 20. We found
astrogliosis in the molecular layer associated with GFAP+ astrocyte hypertrophy and loss of typical
morphology whereas the numbers of GFAP+ astrocytes in the granular cell layer and white matter
were drastically diminished. Furthermore, we found that YY1 differentially alters gene expression
at the later stages of astrocyte development in a region-specific manner and is continuously
needed in mature astrocytes. To test the hypothesis that YY1-dependent chromatin architecture
is critical to execute and sustain programs that affect functions of diverse astrocyte
subpopulations in the cerebellum, we will: 1. Establish the effects of YY1 on the major functions
of subpopulations of cerebellar astrocytes, and 2. Obtain insights into the molecular mechanisms
by which YY1 regulates subpopulations of cerebellar astrocytes.

## Key facts

- **NIH application ID:** 10278047
- **Project number:** 1R01NS122986-01
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** TOMASZ K KORDULA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $460,270
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10278047

## Citation

> US National Institutes of Health, RePORTER application 10278047, Regulation of astrocyte diversity in the cerebellum (1R01NS122986-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10278047. Licensed CC0.

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