# Niche Regulation of Muscle Stem Cells

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $508,578

## Abstract

PROJECT SUMMARY
The niche is a critical regulator of long-term stem cell function. Our long-term goal is to understand the role the
niche plays in regulation of muscle stem cell function. SCs reside in a quiescent state and undergo a series of
transitions as they activate and proliferate. We have identified Wnt4 as a tissue resident inhibitory factor that
represses activation and migration of quiescent satellite cells (QSCs) via Rho-FAK signaling. This is the first
demonstration of a single paracrine acting niche factor coordinates the growth, migration and activation of
QSCs. The overall goal of this proposed study is therefore to understand how Wnt4-Rho-FAK signaling axis
represses activation and migration in QSCs and its implications for SC function in adult and aged mice. The first
aim will combine temporal regulated and cell specific genetic strategies to modulate Wnt4 levels in muscle fibers
to determine the role of Wnt4 (in muscle fibers) and Rho-FAK (in QSCs) on activation and migration in QSCs
and the response to injury. The second aim will dissect the molecular mechanism that prevents QSC activation
and migration via Wnt4. We will examine the role of Wnt4-Rho signaling in the repression of mTORC1 and
Hippo signaling in QSCs. Understanding the role of the niche on SC function will lead to important insights for
cell therapy, muscle degenerative diseases and aging.

## Key facts

- **NIH application ID:** 10427205
- **Project number:** 5R01AR076252-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Andrew S Brack
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $508,578
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427205

## Citation

> US National Institutes of Health, RePORTER application 10427205, Niche Regulation of Muscle Stem Cells (5R01AR076252-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10427205. Licensed CC0.

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