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Development. 2019 Apr 11;146(12). pii: dev174177. doi: 10.1242/dev.174177.

Single cell analysis of adult mouse skeletal muscle stem cells in homeostatic and regenerative conditions.

Author information

1
Genome Technology Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 208292, USA stefania.dell'orso@nih.gov vittorio.sartorelli@nih.gov.
2
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 208292, USA.
3
Genome Technology Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 208292, USA.
4
Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 208292, USA stefania.dell'orso@nih.gov vittorio.sartorelli@nih.gov.

Abstract

Dedicated stem cells ensure postnatal growth, repair and homeostasis of skeletal muscle. Following injury, muscle stem cells (MuSCs) exit from quiescence and divide to reconstitute the stem cell pool and give rise to muscle progenitors. The transcriptomes of pooled MuSCs have provided a rich source of information for describing the genetic programs of distinct static cell states; however, bulk microarray and RNA sequencing provide only averaged gene expression profiles, blurring the heterogeneity and developmental dynamics of asynchronous MuSC populations. Instead, the granularity required to identify distinct cell types, states, and their dynamics can be afforded by single cell analysis. We were able to compare the transcriptomes of thousands of MuSCs and primary myoblasts isolated from homeostatic or regenerating muscles by single cell RNA sequencing. Using computational approaches, we could reconstruct dynamic trajectories and place, in a pseudotemporal manner, the transcriptomes of individual MuSC within these trajectories. This approach allowed for the identification of distinct clusters of MuSCs and primary myoblasts with partially overlapping but distinct transcriptional signatures, as well as the description of metabolic pathways associated with defined MuSC states.

KEYWORDS:

Mouse; Muscle regeneration; Muscle stem cells; Satellite cells; Single cell RNA-seq

PMID:
30890574
PMCID:
PMC6602351
[Available on 2020-06-15]
DOI:
10.1242/dev.174177

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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