scholarly journals Lgr5 Marks Adult Progenitor Cells Contributing to Skeletal Muscle Regeneration and Sarcoma Formation

Cell Reports ◽  
2020 ◽  
Vol 33 (12) ◽  
pp. 108535
Author(s):  
Carly Leung ◽  
Katzrin Bte Ahmad Murad ◽  
Adelyn Liang Thing Tan ◽  
Swathi Yada ◽  
Sowmya Sagiraju ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Progenitor Cells ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration

Rad is temporally regulated within myogenic progenitor cells during skeletal muscle regeneration

2006 ◽  
Vol 290 (2) ◽  
pp. C379-C387 ◽  
Author(s):  
Thomas J. Hawke ◽  
Shane B. Kanatous ◽  
Cindy M. Martin ◽  
Sean C. Goetsch ◽  
Daniel J. Garry
Keyword(s):  
Skeletal Muscle ◽  
Progenitor Cells ◽  
Cell Population ◽  
Muscle Regeneration ◽  
Progenitor Cell ◽  
Transcriptional Activity ◽  
Skeletal Muscle Regeneration ◽  
Progenitor Cell Population ◽  
Myogenic Progenitor Cells ◽  
Myogenic Progenitor

The successful use of myogenic progenitor cells for therapeutic applications requires an understanding of the intrinsic and extrinsic cues involved in their regulation. Herein we demonstrate the expression pattern and transcriptional regulation of Rad, a prototypical member of a family of novel Ras-related GTPases, during mammalian development and skeletal muscle regeneration. Rad was identified using microarray analysis, which revealed robust upregulation of its expression during skeletal muscle regeneration. Our current findings demonstrate negligible Rad expression with resting adult skeletal muscle; however, after muscle injury, Rad is expressed within the myogenic progenitor cell population. Rad expression is significantly increased and localized to the myogenic progenitor cell population during the early phases of regeneration and within the newly regenerated myofibers during the later phases of regeneration. Immunohistochemical analysis demonstrated that Rad and MyoD are coexpressed within the myogenic progenitor cell population of regenerating skeletal muscle. This expression profile of Rad during skeletal muscle regeneration is consistent with the proposed roles for Rad in the inhibition of L-type Ca2+channel activity and the inhibition of Rho/RhoA kinase activity. We also have demonstrated that known myogenic transcription factors (MEF2, MyoD, and Myf-5) can increase the transcriptional activity of the Rad promoter and that this ability is significantly enhanced by the presence of the Ca2+-dependent phosphatase calcineurin. Furthermore, this enhanced transcriptional activity appears to be dependent on the presence of a conserved NFAT binding motif within the Rad promoter. Taken together, these data define Rad as a novel factor within the myogenic progenitor cells of skeletal muscle and identify key regulators of its transcriptional activity.

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.

scholarly journals Stem Cell Aging in Skeletal Muscle Regeneration and Disease

2020 ◽  
Vol 21 (5) ◽  
pp. 1830 ◽  
Author(s):  
Hiroyuki Yamakawa ◽  
Dai Kusumoto ◽  
Hisayuki Hashimoto ◽  
Shinsuke Yuasa
Keyword(s):  
Skeletal Muscle ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Muscle Regeneration ◽  
Muscle Injury ◽  
Skeletal Muscle Regeneration ◽  
Cell Aging ◽  
Regeneration Ability ◽  
Stem Cell Aging ◽  
Muscle Progenitor Cells

Skeletal muscle comprises 30–40% of the weight of a healthy human body and is required for voluntary movements in humans. Mature skeletal muscle is formed by multinuclear cells, which are called myofibers. Formation of myofibers depends on the proliferation, differentiation, and fusion of muscle progenitor cells during development and after injury. Muscle progenitor cells are derived from muscle satellite (stem) cells (MuSCs), which reside on the surface of the myofiber but beneath the basement membrane. MuSCs play a central role in postnatal maintenance, growth, repair, and regeneration of skeletal muscle. In sedentary adult muscle, MuSCs are mitotically quiescent, but are promptly activated in response to muscle injury. Physiological and chronological aging induces MuSC aging, leading to an impaired regenerative capability. Importantly, in pathological situations, repetitive muscle injury induces early impairment of MuSCs due to stem cell aging and leads to early impairment of regeneration ability. In this review, we discuss (1) the role of MuSCs in muscle regeneration, (2) stem cell aging under physiological and pathological conditions, and (3) prospects related to clinical applications of controlling MuSCs.

scholarly journals TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration

2006 ◽  
Vol 25 (24) ◽  
pp. 5826-5839 ◽  
Author(s):  
Mahasweta Girgenrath ◽  
Shawn Weng ◽  
Christine A Kostek ◽  
Beth Browning ◽  
Monica Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Progenitor Cells ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Mesenchymal Progenitor Cells
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