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

Authors

Prech Uapinyoying, Center for Genetic Medicine Research, Children's National Research and Innovation Campus, Children's National Hospital, Washington, DC 20012, 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. Mázala, Center for Genetic Medicine Research, Children's National Research and Innovation Campus, Children's National Hospital, Washington, DC 20012, 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.
Jyoti K. Jaiswal, Center for Genetic Medicine Research, Children's National Research and Innovation Campus, Children's National Hospital, Washington, DC 20012, USA.

Document Type

Journal Article

Publication Date

8-18-2023

Journal

iScience

Volume

26

Issue

8

DOI

10.1016/j.isci.2023.107479

Keywords

Omics; Stem cells research; Transcriptomics

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.

APA Citation

Uapinyoying, Prech; Hogarth, Marshall; Battacharya, Surajit; Mázala, Davi A.; Panchapakesan, Karuna; Bönnemann, Carsten G.; and Jaiswal, Jyoti K., "Single-cell transcriptomic analysis of the identity and function of fibro/adipogenic progenitors in healthy and dystrophic muscle" (2023). GW Authored Works. Paper 3225.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3225

Department

Genomics and Precision Medicine