# Reprogramming and Directed Differentiation of Skeletal Muscle Cells from hPSCs

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $520,463

## Abstract

ABSTRACT
Human pluripotent stem cells (hPSCs) offer enormous potential for understanding human myogenesis and
modeling diseases in a dish. In the previous funding period, we have identified the developmental trajectory of
skeletal muscle progenitor cells (SMPCs) derived from hPSCs to be around embryonic to fetal week 7-12 stage
in human development. We showed that SMPCs do not engraft into the mouse niche efficiently whereas adult
muscle stem cells (SCs) have this robust potential. Further as disease severity increases in mdx mouse models
of Duchenne Muscular Dystrophy we found an increase in aberrant cells in the microenvironment altering robust
engraftment. The next phase of this work in this proposal is now focused on improving our ability to modulate
SMPC and SC states and improve engraftment into the mouse niche as true repopulating stem cells. By using
human development as a model, our work has already yielded significant insights into our understanding of
human myogenesis and the generation of myogenic cells. We will utilize the tools, sequencing datasets and
knowledge gained in the previous funding period to modulate SMPC and SC states and generate a better
therapeutic candidate in this renewal. We will define and functionally validate the key regulatory networks
important for controlling embryonic, fetal SMPCs, or adult SCs and improve our basic knowledge of how
progenitors and stem cells change over time during human myogenesis and from hPSCs (Aim 1). Further we
will evaluate the parameters important for modulating niche occupancy from hPSC SMPCs (Aim 2). This work
will improve our ability to generate a robust stem cell for improved disease modeling and use in regenerative
medicine.

## Key facts

- **NIH application ID:** 10898064
- **Project number:** 5R01AR064327-12
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** April D Pyle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $520,463
- **Award type:** 5
- **Project period:** 2013-09-20 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898064

## Citation

> US National Institutes of Health, RePORTER application 10898064, Reprogramming and Directed Differentiation of Skeletal Muscle Cells from hPSCs (5R01AR064327-12). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10898064. Licensed CC0.

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