# Proliferation competence of skeletal muscle stem cells

> **NIH NIH R01** · CARNEGIE INSTITUTION OF WASHINGTON, D.C. · 2022 · $351,812

## Abstract

PROJECT SUMMARY
Skeletal muscles can regenerate throughout lifetime by using resident muscle stem cells. Muscle stem cells
are normally quiescent. Upon injury stimuli, they can proliferate to make new muscles, i.e. regeneration.
During regeneration, muscle stem cells also renew themselves and return to quiescence so they can foster
future rounds of regeneration. During the aging process and under certain experimental conditions, muscle
stem cells can also break quiescence and proliferate without injury stimuli. However, under these conditions
muscle stem cells do not return to quiescence and become lost. Loss of muscle stem cells negatively impacts
muscle regeneration. What drives muscle stem cells to proliferate without injury pertains to a cellular state of
`proliferation competence' within quiescent muscle stem cells. We are interested in whether the molecular
machinery for this `proliferation competence' during quiescence shares similarity with or differs from injury
stimuli-induced proliferation program.
 We have previously shown that the cyclic-AMP-responsive-element binding protein (CREB) family (CREB,
CREM, and ATF1) of transcriptional activators regulates skeletal myogenic progenitor fate in the mouse
embryo. To test whether the CREB family plays a role in adult muscle regeneration, we inhibited the CREB
family in muscle stem cells. We found that CREB family is need to activate a set of genes in quiescent muscle
stem cells, but not needed to maintain their quiescence. However, muscle stem cells with CREB family
inhibited cannot proliferate or renew following injury stimuli. We identified a protein called Mpp7 as a
candidate mediator acting downstream of CREB family to drive muscle stem cell proliferation and renewal.
We propose that this protein, together with one of its associated protein complexes, constitute common core
machinery for proliferation competence during quiescence and injury-induced proliferation.
 Our proposed research is aimed to determine whether and how Mpp7 instructs muscle stem cell function:
1) We will determine genetically whether Mpp7 is indeed critical for muscle stem cell proliferation and
renewal; 2) We will investigate whether a Mpp7-associated protein complex is responsible for proliferation and
renewal of muscle stem cells using siRNA screens and genetic studies; 3) We will further determine the
biochemical and molecular mechanisms underlying proliferation and renewal of muscle stem cells driven by
the Mpp7-associated protein complex, and explore its potential involvement in mechano-sensing.

## Key facts

- **NIH application ID:** 10401275
- **Project number:** 5R01AR072644-05
- **Recipient organization:** CARNEGIE INSTITUTION OF WASHINGTON, D.C.
- **Principal Investigator:** CHEN-MING FAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $351,812
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401275

## Citation

> US National Institutes of Health, RePORTER application 10401275, Proliferation competence of skeletal muscle stem cells (5R01AR072644-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401275. Licensed CC0.

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