# Exploring networks underlying muscle stem cell identity - Resubmission - 1

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $481,714

## Abstract

Project Summary
 Muscle stem cells, also known as satellite cells (SC), are a progenitor population required to replenish
muscle damaged by exercise or wasting caused by disease or aging. The ability to generate muscle
progenitors from embryonic stem cells (ESC) would represent a major advance in regenerative medicine.
However, despite recent progress, it remains very challenging to differentiate mouse and human ESC into
muscle progenitors, and SC represent a very small population within muscle tissue. These limitations have
significantly hampered progress toward understanding muscle stem cells, and the critical regulatory processes
that govern SC identity. The transcription factor, Pax7, plays a critical role in establishing SC identity, but given
the limitations associated with obtaining SC, our understanding of its molecular function remains incomplete.
We have taken advantage of a system in which Pax7 expression in ESC generates myogenic precursors able
to repopulate the SC niche, and we have begun investigating the chromatin landscape and epigenetic features
of this population to understand its unique properties. With this system, we have shown that Pax7 can
modulate enhancer function and genome topology. Our goal is to understand how a specific chromatin
environment specifies satellite cell identity using state-of-the-art genomic, biochemical, and proteomic
approaches. In two Aims, we will: (I) investigate how Pax7 re-models the genome, packaging chromatin for
long-range interactions; (II) explore how Pax7 collaborates with other factors to establish gene expression and
genome re-wiring in myogenic precursors in vitro and in vivo. We will inactivate a subset of Pax7-associated
factors, enhancers, and identified regulatory elements and examine their functional impact on genome
architecture, gene expression, cell identity, and differentiation.
 It is known that satellite cells are less efficiently renewed during aging, and given that muscle tumors
(rhabdomyosarcomas) aberrantly express Pax7 fusion proteins to maintain muscle in a pre-differentiated state,
our proposal will shed important light on pathological states resulting from aberrant Pax7 activity and stem cell
function.

## Key facts

- **NIH application ID:** 10116803
- **Project number:** 1R01AR076954-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Brian D Dynlacht
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $481,714
- **Award type:** 1
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116803

## Citation

> US National Institutes of Health, RePORTER application 10116803, Exploring networks underlying muscle stem cell identity - Resubmission - 1 (1R01AR076954-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10116803. Licensed CC0.

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