Defining the Skeletal Myogenic Lineage in Human Pluripotent Stem Cell-Derived Teratomas

Matthew P. Pappas, Ning Xie, Jacqueline S Penaloza, Sunny S.K. Chan

Research output: Contribution to journalArticlepeer-review

Abstract

Skeletal muscle stem cells are essential to muscle homeostasis and regeneration after in-jury, and have emerged as a promising cell source for treating skeletal disorders. An attractive ap-proach to obtain these cells utilizes differentiation of pluripotent stem cells (PSCs). We recently re-ported that teratomas derived from mouse PSCs are a rich source of skeletal muscle stem cells. Here, we showed that teratoma formation is also capable of producing skeletal myogenic progenitors from human PSCs. Using single-cell transcriptomics, we discovered several distinct skeletal myogenic subpopulations that represent progressive developmental stages of the skeletal myogenic lineage and recapitulate human embryonic skeletal myogenesis. We further discovered that ERBB3 and CD82 are effective surface markers for prospective isolation of the skeletal myogenic lineage in human PSC-derived teratomas. Therefore, teratoma formation provides an accessible model for ob-taining human skeletal myogenic progenitors from PSCs.

Original languageEnglish (US)
Article number1589
JournalCells
Volume11
Issue number9
DOIs
StatePublished - May 1 2022

Bibliographical note

Funding Information:
Funding: This research was funded by the Regenerative Medicine Minnesota Discovery Science Grant, grant numbers RMM 102516 001 and RMM 092319 DS 003, and the University of Minnesota startup and Children’s Discovery—Winefest funds.

Funding Information:
Acknowledgments: The authors would like to thank Christine Rohlf and Cassandra Schultz for their help with the animal husbandry. We would also like to thank James Dutton at the University of Minnesota for providing 6B4 human iPSCs and PCBC16iPS human iPSCs. The study was supported by the Regenerative Medicine Minnesota Discovery Science Grant (RMM 102516 001, RMM 092319 DS 003) and the University of Minnesota startup and Children’s Discovery—Winefest funds. The monoclonal antibodies to PAX7 and MHC were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • muscle stem cells
  • myogenic development
  • pluripotent stem cells
  • satellite cells

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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