# Skeletal Muscle Regeneration from Pluripotent Stem Cells

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $408,767

## Abstract

Summary
Pluripotent stem cells (ES and iPS cells) have the ability to self-renew and to differentiate into multiple lineages
in vitro. This makes these cells a powerful tool to study early embryonic developmental pathways and to generate
specific cell populations for regenerative medicine and disease investigation. Our research group has pioneered
methods to derive large quantities of skeletal myogenic progenitor cells from mouse and human pluripotent ES
and iPS cells. Upon transplantation into dystrophic mice, these progenitors are not only able to generate new
functional myofibers, but also to seed the satellite cell compartment, thus providing long-term regeneration. With
prior NIH support, we defined the molecular signature of in vitro-generated PSC-derived myogenic progenitors
by comparing their transcriptome profiles to those of primary skeletal myogenic progenitors isolated at different
developmental stages. Our findings revealed that PSC-derived myogenic progenitors possess a molecular
signature similar to embryonic/fetal myoblasts. Paradoxically however, they differ functionally from fetal
myoblasts, as PSC-derived myogenic progenitors show much superior myofiber engraftment and ability to seed
the satellite cell niche, respond to multiple re-injuries and contribute to long-term regeneration. These results led
us to hypothesize that exposure to the adult host skeletal muscle environment may induce molecular changes
in transplanted cells. We found this to be the case as transcriptome analysis of PSC-derived mononuclear cells
(MNCs) re-isolated after engraftment revealed a shift in molecular signature from embryonic/fetal towards
neonatal/adult stages. In this renewal application we propose studies to understand i) the interaction and
molecular cues provided by the adult niche that favor the in vivo maturation of PSC-derived myogenic
progenitors, ii) the role of post-transcriptional regulation in this process, and iii) the dynamics of engraftment and
the quiescence status of specific donor-derived sub-fractions.

## Key facts

- **NIH application ID:** 10869899
- **Project number:** 5R01AR078571-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Rita C. R. Perlingeiro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $408,767
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869899

## Citation

> US National Institutes of Health, RePORTER application 10869899, Skeletal Muscle Regeneration from Pluripotent Stem Cells (5R01AR078571-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10869899. Licensed CC0.

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