Single-cell transcriptomic analysis of the identity and function of fibro/adipogenic progenitors in healthy and dystrophic muscle

Prech Uapinyoying; Marshall Hogarth; Surajit Battacharya; Davi A.G. Mázala; Karuna Panchapakesan; Carsten G. Bönnemann; Jyoti K. Jaiswal

iScience (Aug 2023)

Single-cell transcriptomic analysis of the identity and function of fibro/adipogenic progenitors in healthy and dystrophic muscle

Prech Uapinyoying,
Marshall Hogarth,
Surajit Battacharya,
Davi A.G. Mázala,
Karuna Panchapakesan,
Carsten G. Bönnemann,
Jyoti K. Jaiswal

Affiliations

Prech Uapinyoying: Center for Genetic Medicine Research, Children’s National Research and Innovation Campus, Children’s National Hospital, Washington, DC 20012, USA; Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
Marshall Hogarth: Center for Genetic Medicine Research, Children’s National Research and Innovation Campus, Children’s National Hospital, Washington, DC 20012, USA
Surajit Battacharya: Center for Genetic Medicine Research, Children’s National Research and Innovation Campus, Children’s National Hospital, Washington, DC 20012, USA
Davi A.G. Mázala: Center for Genetic Medicine Research, Children’s National Research and Innovation Campus, Children’s National Hospital, Washington, DC 20012, USA; Department of Kinesiology, College of Health Professions, Towson University, Towson, MD 21252, USA
Karuna Panchapakesan: Center for Genetic Medicine Research, Children’s National Research and Innovation Campus, Children’s National Hospital, Washington, DC 20012, USA
Carsten G. Bönnemann: Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
Jyoti K. Jaiswal: Center for Genetic Medicine Research, Children’s National Research and Innovation Campus, Children’s National Hospital, Washington, DC 20012, USA; Department of Genomics and Precision Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 8
p. 107479

Abstract

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Summary: Fibro/adipogenic progenitors (FAPs) are skeletal muscle stromal cells that support regeneration of injured myofibers and their maintenance in healthy muscles. FAPs are related to mesenchymal stem cells (MSCs/MeSCs) found in other adult tissues, but there is poor understanding of the extent of similarity between these cells. Using single-cell RNA sequencing (scRNA-seq) datasets from multiple mouse tissues, we have performed comparative transcriptomic analysis. This identified remarkable transcriptional similarity between FAPs and MeSCs, confirmed the suitability of PDGFRα as a reporter for FAPs, and identified extracellular proteolysis as a new FAP function. Using PDGFRα as a cell surface marker, we isolated FAPs from healthy and dysferlinopathic mouse muscles and performed scRNA-seq analysis. This revealed decreased FAP-mediated Wnt signaling as a potential driver of FAP dysfunction in dysferlinopathic muscles. Analysis of FAPs in dysferlin- and dystrophin-deficient muscles identified a relationship between the nature of muscle pathology and alteration in FAP gene expression.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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