scholarly journals Noninvasive pulsed focused ultrasound allows spatiotemporal control of targeted homing for multiple stem cell types in murine skeletal muscle and the magnitude of cell homing can be increased through repeated applications

Stem Cells ◽  
2013 ◽  
Vol 31 (11) ◽  
pp. 2551-2560 ◽  
Author(s):  
Scott R. Burks ◽  
Ali Ziadloo ◽  
Saejeong J. Kim ◽  
Ben A. Nguyen ◽  
Joseph A. Frank
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Focused Ultrasound ◽  
Cell Types ◽  
Cell Homing ◽  
Pulsed Focused Ultrasound ◽  
Repeated Applications ◽  
Murine Skeletal Muscle ◽  
Spatiotemporal Control

scholarly journals APC is required for muscle stem cell proliferation and skeletal muscle tissue repair

2015 ◽  
Vol 210 (5) ◽  
pp. 717-726 ◽  
Author(s):  
Alice Parisi ◽  
Floriane Lacour ◽  
Lorenzo Giordani ◽  
Sabine Colnot ◽  
Pascal Maire ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Cell Cycle Progression ◽  
Cell Types ◽  
Double Knockout ◽  
Muscle Stem Cells ◽  
Adult Muscle ◽  
Canonical Wnt

The tumor suppressor adenomatous polyposis coli (APC) is a crucial regulator of many stem cell types. In constantly cycling stem cells of fast turnover tissues, APC loss results in the constitutive activation of a Wnt target gene program that massively increases proliferation and leads to malignant transformation. However, APC function in skeletal muscle, a tissue with a low turnover rate, has never been investigated. Here we show that conditional genetic disruption of APC in adult muscle stem cells results in the abrogation of adult muscle regenerative potential. We demonstrate that APC removal in adult muscle stem cells abolishes cell cycle entry and leads to cell death. By using double knockout strategies, we further prove that this phenotype is attributable to overactivation of β-catenin signaling. Our results demonstrate that in muscle stem cells, APC dampens canonical Wnt signaling to allow cell cycle progression and radically diverge from previous observations concerning stem cells in actively self-renewing tissues.

scholarly journals MR‐guided pulsed focused ultrasound improves mesenchymal stromal cell homing to the myocardium

2020 ◽  
Vol 24 (22) ◽  
pp. 13278-13288
Author(s):  
Kee W. Jang ◽  
Tsang‐Wei Tu ◽  
Robert B. Rosenblatt ◽  
Scott R. Burks ◽  
Joseph A. Frank
Keyword(s):  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Focused Ultrasound ◽  
Cell Homing ◽  
Pulsed Focused Ultrasound

scholarly journals Sca1+ cells as direct isolate (ex vivo) versus in vitro cultured exhibit differential proteomic signatures in murine skeletal muscle

2020 ◽  
Author(s):  
Saketh Kapoor ◽  
Pratigya Subba ◽  
Sudheer Shenoy P ◽  
Bipasha Bose
Keyword(s):  
Skeletal Muscle ◽  
Muscle Development ◽  
High Resolution Mass Spectrometry ◽  
Ex Vivo ◽  
Cell Types ◽  
Molecular Networks ◽  
Cellular Microenvironments ◽  
Murine Skeletal Muscle ◽  
The Impact

AbstractStem cell antigen-1 (Sca-1) is a glycosyl-phosphatidylinositol-anchored membrane protein that is expressed in a sub-population of muscle stem and progenitor cell types. Reportedly, Sca-1 regulates the myogenic property of myoblasts and Sca-1-/- mice exhibited defective muscle regeneration. Although the role of Sca-1 in muscle development and maintenance is well-acknowledged, molecular composition of muscle derived Sca-1+ cells is not characterized. Here, we applied a high-resolution mass spectrometry-based workflow to characterize the proteomic landscape of mouse hindlimb skeletal muscle derived Sca-1+ cells. Furthermore, we characterized the impact of the cellular microenvironments on the proteomes of Sca-1+ cells. The proteome component of freshly isolated (ex vivo) Sca-1+ cells was compared with that of Sca-1+ cells expanded in cell culture (in vitro). The analysis revealed significant differences in the protein abundances in the two conditions reflective of their functional variations. The identified proteins were enriched in various biological pathways. Notably, we identified proteins related to myotube differentiation, myotube cell development and myoblast fusion. We also identified a panel of cell surface marker proteins that can be leveraged in future to enrich Sca-1+ cells using combinatorial strategies. Comparative analysis implicated the activation of various pathways leading to increased protein synthesis under in vitro condition. We report here the most comprehensive proteome map of Sca-1+ cells that provides insights into the molecular networks operative in Sca-1+ cells. Importantly, through our work we generated the proteomic blueprint of protein abundances significantly altered in Sca-1+ cells under ex vivo and in vitro conditions.

scholarly journals A Promising Future for Stem-Cell-Based Therapies in Muscular Dystrophies—In Vitro and In Vivo Treatments to Boost Cellular Engraftment

2019 ◽  
Vol 20 (21) ◽  
pp. 5433 ◽  
Author(s):  
Daniela Gois Beghini ◽  
Samuel Iwao Horita ◽  
Liana Monteiro da Fonseca Cardoso ◽  
Luiz Anastacio Alves ◽  
Kanneboyina Nagaraju ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Genetic Diseases ◽  
Life Quality ◽  
Cell Types ◽  
Genetic Alterations ◽  
Skeletal Muscle Regeneration ◽  
Muscular Dystrophies

Muscular dystrophies (MD) are a group of genetic diseases that lead to skeletal muscle wasting and may affect many organs (multisystem). Unfortunately, no curative therapies are available at present for MD patients, and current treatments mainly address the symptoms. Thus, stem-cell-based therapies may present hope for improvement of life quality and expectancy. Different stem cell types lead to skeletal muscle regeneration and they have potential to be used for cellular therapies, although with several limitations. In this review, we propose a combination of genetic, biochemical, and cell culture treatments to correct pathogenic genetic alterations and to increase proliferation, dispersion, fusion, and differentiation into new or hybrid myotubes. These boosted stem cells can also be injected into pretreate recipient muscles to improve engraftment. We believe that this combination of treatments targeting the limitations of stem-cell-based therapies may result in safer and more efficient therapies for MD patients. Matricryptins have also discussed.

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

2019 ◽  
Author(s):  
Andrea J. De Micheli ◽  
Paula Fraczek ◽  
Sharon Soueid-Baumgarten ◽  
Hiranmayi Ravichandran ◽  
Iwijn De Vlaminck ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Single Cell ◽  
Progenitor Cells ◽  
Muscle Regeneration ◽  
Cell Types ◽  
Myogenic Cell ◽  
Skeletal Muscle Regeneration ◽  
Cell Populations ◽  
Communication Signals

AbstractMuscle stem cells (MuSCs) are an essential adult stem cell population with the capacity to self-renew and regenerate muscle tissue. Functionally heterogeneous subpopulations of MuSCs have been identified based on their expression of myogenic regulatory factors and surface markers. However, a unified organization of muscle stem and progenitor cells and their subpopulations remains unresolved. Here, we performed temporal analysis of skeletal muscle regeneration using single-cell RNA-sequencing (scRNA-seq) of myotoxin-injured adult mouse hindlimb muscles. We generated over 34,000 single-cell transcriptomes spanning four muscle regeneration time-points and identified 15 distinct cell types, including a heterogeneous population of MuSCs and progenitor cells. Our analysis provides a hierarchical map of myogenic cell populations and identifies stage-specific regulatory programs that govern their contributions to muscle regeneration. In this transcriptomic atlas, we observed cell type-specific regenerative dynamics, exemplified by waves of transient amplification and diversification of multiple immune cell types and, subsequently, myogenic cells. Unbiased trajectory inference organized the myogenic cell populations within the atlas into a continuum, consisting of a hierarchy of quiescent MuSCs, cycling progenitors, committed myoblasts, and terminally differentiated myocytes. This myogenic trajectory matched prior understanding and also revealed that MuSC stages are defined by synchronous changes in regulatory factors, cell cycle-associated, and surface receptor gene expression. Lastly, we analyzed the transcriptomic atlas to identify over 100 candidate heterotypic communication signals between myogenic and non-myogenic cell populations, including many involving the fibroblast growth factor (FGF), Notch, and Syndecan receptor families and their associated ligands. Syndecan receptors were implicated in a large fraction of these cell communication interactions and were observed to exhibit transcriptional heterogeneity within the myogenic continuum. Using multiparameter mass cytometry (CyTOF), we confirmed that cycling MuSCs exhibit diversified Syndecan-1/2 expression, which suggests that dynamic alterations in Syndecan signaling interactions may coordinate stage-specific myogenic cell fate regulation. This scRNA-seq reference atlas provides a resolved hierarchical organization of myogenic subpopulations as a resource to investigate cell-cell interactions that regulate myogenic stem and progenitor cell fates in muscle regeneration.

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