[PDF][PDF] Single-cell analysis of the muscle stem cell hierarchy identifies heterotypic communication signals involved in skeletal muscle regeneration

AJ De Micheli, EJ Laurilliard, CL Heinke… - Cell reports, 2020 - cell.com
AJ De Micheli, EJ Laurilliard, CL Heinke, H Ravichandran, P Fraczek, S Soueid-Baumgarten…
Cell reports, 2020cell.com
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 …
Summary
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.
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