# Skeletal Muscle Regeneration from Pluripotent Stem Cells

> **NIH NIH R56** · UNIVERSITY OF MINNESOTA · 2020 · $423,792

## 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. Supported by R01 AR055299, 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. In the last funding period, we defined the molecular signature of in vitro-
generated PS cell-derived myogenic progenitors by comparing their transcriptome profiles to those of primary
skeletal myogenic progenitors isolated at different developmental stages. Our findings revealed that PS cell-
derived myogenic progenitors possess a molecular signature similar to embryonic/fetal myoblasts. Paradoxically
however, they differ functionally from fetal myoblasts, as PS cell-derived myogenic progenitors show much
superior myofiber engraftment and ability to seed the satellite cell compartment, 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 PS cell-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 PS cell-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:** 10255091
- **Project number:** 2R56AR055299-11A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Rita C. R. Perlingeiro
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,792
- **Award type:** 2
- **Project period:** 2008-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10255091

## Citation

> US National Institutes of Health, RePORTER application 10255091, Skeletal Muscle Regeneration from Pluripotent Stem Cells (2R56AR055299-11A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10255091. Licensed CC0.

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