scholarly journals R-spondin1 regulates muscle progenitor cell fusion through control of antagonist Wnt signaling pathways

2016 ◽  
Author(s):  
Floriane Lacour ◽  
Elsa Vezin ◽  
Florian Bentzinger ◽  
Marie-Claude Sincennes ◽  
Robert D. Mitchell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Wnt Signaling ◽  
Signaling Pathways ◽  
Muscle Regeneration ◽  
Muscle Cells ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury ◽  
Canonical Wnt

SUMMARYTissue regeneration requires the selective activation and repression of specific signaling pathways in stem cells. As such, the Wnt signaling pathways have been shown to control stem cell fate. In many cell types, the R-Spondin (Rspo) family of secreted proteins acts as potent activators of the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. Firstly we show that Rspo1-null muscles do not display any abnormalities at the basal level. However deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We found that muscle stem cells lacking Rspo1 show delayed differentiation. Transcriptome analysis further demonstrated that Rspo1 is required for the activation of Wnt/β-catenin target genes in muscle cells. Furthermore, muscle cells lacking Rspo1 fuse with a higher frequency than normal cells, leading to larger myotubes containing more nuclei both in vitro and in vivo. We found the increase in muscle fusion was dependent on up-regulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that antagonistic control of canonical and non-canonical Wnt signaling pathways by Rspo1 in muscle stem cell progeny is important for restitution of normal muscle architecture during skeletal muscle regeneration.

P.131Cytoglobin modulates skeletal muscle regeneration by targeting canonical Wnt signaling

2019 ◽  
Vol 29 ◽  
pp. S86
Author(s):  
S. Singh ◽  
J. Haung ◽  
D. Rivas ◽  
T. Gemelli ◽  
M. Weiler ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Wnt Signaling ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Canonical Wnt Signaling ◽  
Canonical Wnt

scholarly journals Long-Term Self-Renewal of Postnatal Muscle-derived Stem Cells

2005 ◽  
Vol 16 (7) ◽  
pp. 3323-3333 ◽  
Author(s):  
B. M. Deasy ◽  
B. M. Gharaibeh ◽  
J. B. Pollett ◽  
M. M. Jones ◽  
M. A. Lucas ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Muscle Regeneration ◽  
Replicative Senescence ◽  
Skeletal Muscle Regeneration ◽  
Cell Aging ◽  
Mdx Mice ◽  
Self Renewal

The ability to undergo self-renewal is a defining characteristic of stem cells. Self-replenishing activity sustains tissue homeostasis and regeneration. In addition, stem cell therapy strategies require a heightened understanding of the basis of the self-renewal process to enable researchers and clinicians to obtain sufficient numbers of undifferentiated stem cells for cell and gene therapy. Here, we used postnatal muscle-derived stem cells to test the basic biological assumption of unlimited stem cell replication. Muscle-derived stem cells (MDSCs) expanded for 300 population doublings (PDs) showed no indication of replicative senescence. MDSCs preserved their phenotype (ScaI+/CD34+/desminlow) for 200 PDs and were capable of serial transplantation into the skeletal muscle of mdx mice, which model Duchenne muscular dystrophy. MDSCs expanded to this level exhibited high skeletal muscle regeneration comparable with that exhibited by minimally expanded cells. Expansion beyond 200 PDs resulted in lower muscle regeneration, loss of CD34 expression, loss of myogenic activity, and increased growth on soft agar, suggestive of inevitable cell aging attributable to expansion and possible transformation of the MDSCs. Although these results raise questions as to whether cellular transformations derive from cell culturing or provide evidence of cancer stem cells, they establish the remarkable long-term self-renewal and regeneration capacity of postnatal MDSCs.

scholarly journals Fibro-adipogenic progenitors in skeletal muscle homeostasis, regeneration and diseases

Open Biology ◽  
2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Thomas Molina ◽  
Paul Fabre ◽  
Nicolas A. Dumont
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscle Regeneration ◽  
New Technologies ◽  
Cell Activity ◽  
Cellular Heterogeneity ◽  
Skeletal Muscle Regeneration ◽  
Acute Injury ◽  
Muscle Stem Cells ◽  
Muscle Homeostasis

Skeletal muscle possesses a remarkable regenerative capacity that relies on the activity of muscle stem cells, also known as satellite cells. The presence of non-myogenic cells also plays a key role in the coordination of skeletal muscle regeneration. Particularly, fibro-adipogenic progenitors (FAPs) emerged as master regulators of muscle stem cell function and skeletal muscle regeneration. This population of muscle resident mesenchymal stromal cells has been initially characterized based on its bi-potent ability to differentiate into fibroblasts or adipocytes. New technologies such as single-cell RNAseq revealed the cellular heterogeneity of FAPs and their complex regulatory network during muscle regeneration. In acute injury, FAPs rapidly enter the cell cycle and secrete trophic factors that support the myogenic activity of muscle stem cells. Conversely, deregulation of FAP cell activity is associated with the accumulation of fibrofatty tissue in pathological conditions such as muscular dystrophies and ageing. Considering their central role in skeletal muscle pathophysiology, the regulatory mechanisms of FAPs and their cellular and molecular crosstalk with muscle stem cells are highly investigated in the field. In this review, we summarize the current knowledge on FAP cell characteristics, heterogeneity and the cellular crosstalk during skeletal muscle homeostasis and regeneration. We further describe their role in muscular disorders, as well as different therapeutic strategies targeting these cells to restore muscle regeneration.

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.

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
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