scholarly journals A cellular atlas of skeletal muscle regeneration and aging

2019 ◽  
Author(s):  
Bradley Pawlikowski ◽  
Nicole Dalla Betta ◽  
Tiffany Elston ◽  
Rebecca O’Rourke ◽  
Kenneth Jones ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Muscle Regeneration ◽  
Muscle Function ◽  
Immune Cell ◽  
Complex Structure ◽  
Skeletal Muscle Regeneration ◽  
Nerve Tissue ◽  
Post Injury ◽  
Muscle Stem Cell

SummaryAn individual skeletal muscle is a complex structure, composed of large contractile myofibers, connective tissue, nerve tissue, immune cells, stem cells and the vasculature. Each of these components contribute to skeletal muscle function, maintenance, regeneration, and if perturbed can potentially contribute to or cause disease that reduces muscle function. To investigate the cellular inventory of skeletal muscle we carried out single cell RNA sequencing on cells isolated from adult uninjured muscle, adult post injury muscle, and from aged uninjured muscle. Our muscle atlas provides the cellular landscape and partial transcriptome of pre-injury, post injury, and aged muscle, identifying dramatic changes in the muscle stem cell, fibroblast and immune cell populations during regeneration. Our data highlight dynamic changes occurring during muscle regeneration, identify potential extrinsic mechanisms that control muscle stem cell behavior, and underscore the inflamed state of aged uninjured muscle.

scholarly journals Single-Cell Analysis of the Muscle Stem Cell Hierarchy Identifies Heterotypic Communication Signals Involved in Skeletal Muscle Regeneration

Cell Reports ◽  
2020 ◽  
Vol 30 (10) ◽  
pp. 3583-3595.e5 ◽  
Author(s):  
Andrea J. De Micheli ◽  
Emily J. Laurilliard ◽  
Charles L. Heinke ◽  
Hiranmayi Ravichandran ◽  
Paula Fraczek ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Single Cell ◽  
Muscle Regeneration ◽  
Single Cell Analysis ◽  
Skeletal Muscle Regeneration ◽  
Cell Analysis ◽  
Muscle Stem Cell ◽  
Communication Signals ◽  
Stem Cell Hierarchy

scholarly journals Progressive and Coordinated Mobilization of the Skeletal Muscle Niche throughout Tissue Repair Revealed by Single-Cell Proteomic Analysis

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 744
Author(s):  
Matthew Borok ◽  
Nathalie Didier ◽  
Francesca Gattazzo ◽  
Teoman Ozturk ◽  
Aurelien Corneau ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Muscle Regeneration ◽  
Cell Types ◽  
Skeletal Muscle Regeneration ◽  
Muscle Repair ◽  
Muscle Stem Cell ◽  
Muscle Stem Cells ◽  
Cell Lineages

Background: Skeletal muscle is one of the only mammalian tissues capable of rapid and efficient regeneration after trauma or in pathological conditions. Skeletal muscle regeneration is driven by the muscle satellite cells, the stem cell population in interaction with their niche. Upon injury, muscle fibers undergo necrosis and muscle stem cells activate, proliferate and fuse to form new myofibers. In addition to myogenic cell populations, interaction with other cell types such as inflammatory cells, mesenchymal (fibroadipogenic progenitors—FAPs, pericytes) and vascular (endothelial) lineages are important for efficient muscle repair. While the role of the distinct populations involved in skeletal muscle regeneration is well characterized, the quantitative changes in the muscle stem cell and niche during the regeneration process remain poorly characterized. Methods: We have used mass cytometry to follow the main muscle cell types (muscle stem cells, vascular, mesenchymal and immune cell lineages) during early activation and over the course of muscle regeneration at D0, D2, D5 and D7 compared with uninjured muscles. Results: Early activation induces a number of rapid changes in the proteome of multiple cell types. Following the induction of damage, we observe a drastic loss of myogenic, vascular and mesenchymal cell lineages while immune cells invade the damaged tissue to clear debris and promote muscle repair. Immune cells constitute up to 80% of the mononuclear cells 5 days post-injury. We show that muscle stem cells are quickly activated in order to form new myofibers and reconstitute the quiescent muscle stem cell pool. In addition, our study provides a quantitative analysis of the various myogenic populations during muscle repair. Conclusions: We have developed a mass cytometry panel to investigate the dynamic nature of muscle regeneration at a single-cell level. Using our panel, we have identified early changes in the proteome of stressed satellite and niche cells. We have also quantified changes in the major cell types of skeletal muscle during regeneration and analyzed myogenic transcription factor expression in satellite cells throughout this process. Our results highlight the progressive dynamic shifts in cell populations and the distinct states of muscle stem cells adopted during skeletal muscle regeneration. Our findings give a deeper understanding of the cellular and molecular aspects of muscle regeneration.

scholarly journals Satellite Cells and the Muscle Stem Cell Niche

2013 ◽  
Vol 93 (1) ◽  
pp. 23-67 ◽  
Author(s):  
Hang Yin ◽  
Feodor Price ◽  
Michael A. Rudnicki
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Stem Cell Niche ◽  
Skeletal Muscle Regeneration ◽  
Stem Cell Population ◽  
Muscle Stem Cell ◽  
Adult Skeletal Muscle ◽  
Cell Niche

Adult skeletal muscle in mammals is a stable tissue under normal circumstances but has remarkable ability to repair after injury. Skeletal muscle regeneration is a highly orchestrated process involving the activation of various cellular and molecular responses. As skeletal muscle stem cells, satellite cells play an indispensible role in this process. The self-renewing proliferation of satellite cells not only maintains the stem cell population but also provides numerous myogenic cells, which proliferate, differentiate, fuse, and lead to new myofiber formation and reconstitution of a functional contractile apparatus. The complex behavior of satellite cells during skeletal muscle regeneration is tightly regulated through the dynamic interplay between intrinsic factors within satellite cells and extrinsic factors constituting the muscle stem cell niche/microenvironment. For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved our understanding of skeletal muscle biology. Here, we review some recent advances, with focuses on functions of satellite cells and their niche during the process of skeletal muscle regeneration.

Mesenchymal-stem-cell-derived exosomes accelerate skeletal muscle regeneration

FEBS Letters ◽  
2015 ◽  
Vol 589 (11) ◽  
pp. 1257-1265 ◽  
Author(s):  
Yoshihiro Nakamura ◽  
Shigeru Miyaki ◽  
Hiroyuki Ishitobi ◽  
Sho Matsuyama ◽  
Tomoyuki Nakasa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration

scholarly journals Tumor Necrosis Factor-α Inhibition of Skeletal Muscle Regeneration Is Mediated by a Caspase-Dependent Stem Cell Response

Stem Cells ◽  
2008 ◽  
Vol 26 (4) ◽  
pp. 997-1008 ◽  
Author(s):  
Viviana Moresi ◽  
Alessandro Pristerà ◽  
Bianca M. Scicchitano ◽  
Mario Molinaro ◽  
Laura Teodori ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Tumor Necrosis Factor ◽  
Muscle Regeneration ◽  
Cell Response ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Skeletal Muscle Regeneration ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Skeletal muscle stem cell self-renewal and differentiation kinetics revealed by EdU lineage tracing during regeneration

2019 ◽  
Author(s):  
Bradley Pawlikowski ◽  
Nicole Dalla Betta ◽  
Tiffany Antwine ◽  
Bradley B. Olwin
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Young Adult ◽  
Muscle Injury ◽  
Lineage Tracing ◽  
Stem Cell Population ◽  
Post Injury ◽  
Self Renewal ◽  
Muscle Stem Cell

SummarySkeletal muscle maintenance and repair is dependent on the resident adult muscle stem cell (MuSC). During injury, and in diseased muscle, stem cells are engaged to replace or repair damaged muscle, which requires the stem cells to exit quiescence and expand, followed by differentiation to regenerate myofibers and self-renewal to replenish the stem cell population. Following an injury, little is known regarding the timing of MuSC (skeletal muscle stem cell) self-renewal, myoblast expansion or myoblast differentiation. To determine the timing and kinetics of these cell fate decisions, we employed DNA-based lineage tracing to label newly replicated cells and followed cell fates during skeletal muscle regeneration. MuSCs activate and expand as myoblasts rapidly following injury, where the majority differentiate into myonuclei, establishing the centrally located myonuclear pool. Re-establishing the majority MuSC pool by self-renewal occurs after 5 days post-muscle injury, accompanied by low levels of myonuclear accretion that generate only peripheral myonuclei. In aged mice, possessing ∼1/2 the number of MuSCs present in young adult mice, the timing of post injury MuSC self-renewal is delayed, and although MuSCs expansion as myoblasts in aged muscle is impaired, the number of MuSC unexpectedly recovers to young adult levels during regeneration. Following an induced muscle injury, we found that myonuclei are generated within the first four days post injury derived from myoblasts expanding from activated MuSCs. Only later during regeneration, from 5 d to 14 d post injury, is the MuSC pool replenished by self-renewal, accompanied by generation of peripheral myonuclei.

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