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

doi:10.1016/j.isci.2023.107479

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

iScience. 2023 Jul 23;26(8):107479. doi: 10.1016/j.isci.2023.107479. eCollection 2023 Aug 18.

Authors

Prech Uapinyoying^{1

2}, Marshall Hogarth¹, Surajit Battacharya¹, Davi A G Mázala^{1

3}, Karuna Panchapakesan¹, Carsten G Bönnemann², Jyoti K Jaiswal^{1

4}

Affiliations

¹ Center for Genetic Medicine Research, Children's National Research and Innovation Campus, Children's National Hospital, Washington, DC 20012, USA.
² Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
³ Department of Kinesiology, College of Health Professions, Towson University, Towson, MD 21252, USA.
⁴ Department of Genomics and Precision Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC 20052, USA.

Abstract

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.

Keywords: Omics; Stem cells research; Transcriptomics.

Grants and funding

R01 AR055686/AR/NIAMS NIH HHS/United States