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

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.

2005 ◽  
Vol 16 (7) ◽  
pp. 3323-3333 ◽  
Author(s):  
B. M. Deasy ◽  
B. M. Gharaibeh ◽  
J. B. Pollett ◽  
M. M. Jones ◽  
M. A. Lucas ◽  
...  

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.


2019 ◽  
Author(s):  
Andrea J. De Micheli ◽  
Paula Fraczek ◽  
Sharon Soueid-Baumgarten ◽  
Hiranmayi Ravichandran ◽  
Iwijn De Vlaminck ◽  
...  

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.


2012 ◽  
Vol 1 (1) ◽  
pp. 151-154 ◽  
Author(s):  
Norio Motohashi ◽  
Matthew S. Alexander ◽  
Louis M. Kunkel

FEBS Letters ◽  
2015 ◽  
Vol 589 (11) ◽  
pp. 1257-1265 ◽  
Author(s):  
Yoshihiro Nakamura ◽  
Shigeru Miyaki ◽  
Hiroyuki Ishitobi ◽  
Sho Matsuyama ◽  
Tomoyuki Nakasa ◽  
...  

2021 ◽  
pp. 2007946
Author(s):  
Yoonhee Jin ◽  
Dena Shahriari ◽  
Eun Je Jeon ◽  
Seongjun Park ◽  
Yi Sun Choi ◽  
...  

2021 ◽  
pp. 101528
Author(s):  
Xiaotong Hong ◽  
Silvia Campanario ◽  
Ramirez-PardoIgnacio Ramírez-Pardo ◽  
Grima-TerrenMercedes Grima-Terrén ◽  
Joan Isern ◽  
...  

2021 ◽  
Author(s):  
Kentaro Fukuda ◽  
Taisuke Kuroda ◽  
Norihisa Tamura ◽  
Hiroshi Mita ◽  
Hirofumi Miyata ◽  
...  

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