期刊
SKELETAL MUSCLE
卷 10, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13395-020-00236-3
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资金
- National Institutes of Health [R01AG058630]
- Glenn Medical Research Foundation
- American Federation for Aging Research Grant for Junior Faculty
- US Department of Education Graduate Assistantship in Areas of National Need [P200A150273]
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 similar to 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 theEGFRreceptor, 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.
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