A reference single-cell transcriptomic atlas of human skeletal muscle tissue reveals bifurcated muscle stem cell populations.

TitleA reference single-cell transcriptomic atlas of human skeletal muscle tissue reveals bifurcated muscle stem cell populations.
Publication TypeJournal Article
Year of Publication2020
AuthorsDe Micheli AJ, Spector JA, Elemento O, Cosgrove BD
JournalSkelet Muscle
Volume10
Issue1
Pagination19
Date Published2020 Jul 06
ISSN2044-5040
Abstract

Single-cell RNA-sequencing (scRNA-seq) facilitates the unbiased reconstruction of multicellular tissue systems in health and disease. Here, we present a curated scRNA-seq dataset of human muscle samples from 10 adult donors with diverse anatomical locations. We integrated ~ 22,000 single-cell transcriptomes using Scanorama to account for technical and biological variation and resolved 16 distinct populations of muscle-resident cells using unsupervised clustering of the data compendium. These cell populations included muscle stem/progenitor cells (MuSCs), which bifurcated into discrete "quiescent" and "early-activated" MuSC subpopulations. Differential expression analysis identified transcriptional profiles altered in the activated MuSCs including genes associated with aging, obesity, diabetes, and impaired muscle regeneration, as well as long non-coding RNAs previously undescribed in human myogenic cells. Further, we modeled ligand-receptor cell-communication interactions and observed enrichment of the TWEAK-FN14 pathway in activated MuSCs, a characteristic signature of muscle wasting diseases. In contrast, the quiescent MuSCs have enhanced expression of the EGFR receptor, a recognized human MuSC marker. This work provides a new benchmark reference resource to examine human muscle tissue heterogeneity and identify potential targets in MuSC diversity and dysregulation in disease contexts.

DOI10.1186/s13395-020-00236-3
Alternate JournalSkelet Muscle
PubMed ID32624006
PubMed Central IDPMC7336639
Grant ListR01AG058630 / AG / NIA NIH HHS / United States
Grant for Junior Faculty / / American Federation for Aging Research /
P200A150273 / / U.S. Department of Education /