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

Matthew P Pappas; Ning Xie; Jacqueline S Penaloza; Sunny S K Chan

doi:10.3390/cells11091589

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

Cells. 2022 May 9;11(9):1589. doi: 10.3390/cells11091589.

Authors

Matthew P Pappas¹, Ning Xie¹, Jacqueline S Penaloza¹, Sunny S K Chan^{1

2

3}

Affiliations

¹ Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
² Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
³ Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA.

Abstract

Skeletal muscle stem cells are essential to muscle homeostasis and regeneration after injury, and have emerged as a promising cell source for treating skeletal disorders. An attractive approach to obtain these cells utilizes differentiation of pluripotent stem cells (PSCs). We recently reported 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 obtaining human skeletal myogenic progenitors from PSCs.

Keywords: muscle stem cells; myogenic development; pluripotent stem cells; satellite cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Mice
Muscle Development / physiology
Muscle Fibers, Skeletal / metabolism
Muscle, Skeletal
Pluripotent Stem Cells* / metabolism
Teratoma*

Grants and 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.