1. Single-Cell Analysis of the Muscle Stem Cell Hierarchy Identifies Heterotypic Communication Signals Involved in Skeletal Muscle Regeneration.
- Author
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De Micheli AJ, Laurilliard EJ, Heinke CL, Ravichandran H, Fraczek P, Soueid-Baumgarten S, De Vlaminck I, Elemento O, and Cosgrove BD
- Subjects
- Adipogenesis genetics, Animals, Cell Proliferation, Gene Expression Regulation, Ligands, Mice, Inbred C57BL, Models, Biological, Muscle Development genetics, Paracrine Communication, RNA-Seq, Receptors, Cell Surface metabolism, Syndecans metabolism, Cell Communication, Muscle, Skeletal cytology, Muscle, Skeletal physiology, Regeneration, Signal Transduction, Single-Cell Analysis, Stem Cells metabolism
- Abstract
Muscle regeneration relies on the regulation of muscle stem cells (MuSCs) through paracrine signaling interactions. We analyzed muscle regeneration in mice using single-cell RNA sequencing (scRNA-seq) and generated over 34,000 single-cell transcriptomes spanning four time-points. We identified 15 distinct cell types including heterogenous populations of muscle stem and progenitor cells. We resolved a hierarchical map of these myogenic cells by trajectory inference and observed stage-specific regulatory programs within this continuum. Through ligand-receptor interaction analysis, we identified over 100 candidate regeneration-associated paracrine communication pairs between MuSCs and non-myogenic cells. We show that myogenic stem/progenitor cells exhibit heterogeneous expression of multiple Syndecan proteins in cycling myogenic cells, suggesting that Syndecans may coordinate myogenic fate regulation. We performed ligand stimulation in vitro and confirmed that three paracrine factors (FGF2, TGFβ1, and RSPO3) regulate myogenic cell proliferation in a Syndecan-dependent manner. Our study provides a scRNA-seq reference resource to investigate cell communication interactions in muscle regeneration., Competing Interests: Declaration of Interests The authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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