A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells

Haibin Xi; Justin Langerman; Shan Sabri; Peggie Chien; Courtney S Young; Shahab Younesi; Michael Hicks; Karen Gonzalez; Wakana Fujiwara; Julia Marzi; Simone Liebscher; Melissa Spencer; Ben Van Handel; Denis Evseenko; Katja Schenke-Layland; Kathrin Plath; April D Pyle

doi:10.1016/j.stem.2020.04.017

A Human Skeletal Muscle Atlas Identifies the Trajectories of Stem and Progenitor Cells across Development and from Human Pluripotent Stem Cells

Cell Stem Cell. 2020 Jul 2;27(1):158-176.e10. doi: 10.1016/j.stem.2020.04.017. Epub 2020 May 11.

Authors

Haibin Xi¹, Justin Langerman², Shan Sabri², Peggie Chien³, Courtney S Young⁴, Shahab Younesi¹, Michael Hicks¹, Karen Gonzalez⁵, Wakana Fujiwara⁶, Julia Marzi⁷, Simone Liebscher⁸, Melissa Spencer⁹, Ben Van Handel¹⁰, Denis Evseenko¹⁰, Katja Schenke-Layland¹¹, Kathrin Plath¹², April D Pyle¹³

Affiliations

¹ Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA.
² Deparment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
³ Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
⁵ Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.
⁶ Department of Biochemistry, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ Department of Women's Health, Research Institute for Women's Health, Eberhard Karls University Tübingen, Tübingen, Germany; The Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany.
⁸ Department of Women's Health, Research Institute for Women's Health, Eberhard Karls University Tübingen, Tübingen, Germany.
⁹ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
¹⁰ Department of Orthopaedic Surgery, Keck School of Medicine, Stem Cell Research and Regenerative Medicine, University of Southern California, Los Angeles, CA, USA.
¹¹ Department of Women's Health, Research Institute for Women's Health, Eberhard Karls University Tübingen, Tübingen, Germany; The Natural and Medical Sciences Institute (NMI) at the University of Tübingen, Reutlingen, Germany; Department of Medicine/Cardiology, Cardiovascular Research Laboratories, University of California, Los Angeles, Los Angeles, CA, USA.
¹² Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Deparment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: kplath@mednet.ucla.edu.
¹³ Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: apyle@mednet.ucla.edu.

Abstract

The developmental trajectory of human skeletal myogenesis and the transition between progenitor and stem cell states are unclear. We used single-cell RNA sequencing to profile human skeletal muscle tissues from embryonic, fetal, and postnatal stages. In silico, we identified myogenic as well as other cell types and constructed a "roadmap" of human skeletal muscle ontogeny across development. In a similar fashion, we also profiled the heterogeneous cell cultures generated from multiple human pluripotent stem cell (hPSC) myogenic differentiation protocols and mapped hPSC-derived myogenic progenitors to an embryonic-to-fetal transition period. We found differentially enriched biological processes and discovered co-regulated gene networks and transcription factors present at distinct myogenic stages. This work serves as a resource for advancing our knowledge of human myogenesis. It also provides a tool for a better understanding of hPSC-derived myogenic progenitors for translational applications in skeletal muscle-based regenerative medicine.

Keywords: development; human myogenesis; pluripotent stem cells; satellite cells; single cell RNA-sequencing; skeletal muscle.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation
Humans
Muscle Development*
Muscle, Skeletal
Pluripotent Stem Cells*
Transcription Factors

Substances

Transcription Factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding