scholarly journals Six1 regulates stem cell repair potential and self-renewal during skeletal muscle regeneration

2012 ◽  
Vol 198 (5) ◽  
pp. 815-832 ◽  
Author(s):  
Fabien Le Grand ◽  
Raphaëlle Grifone ◽  
Philippos Mourikis ◽  
Christophe Houbron ◽  
Carine Gigaud ◽  
...  

Satellite cells (SCs) are stem cells that mediate skeletal muscle growth and regeneration. Here, we observe that adult quiescent SCs and their activated descendants expressed the homeodomain transcription factor Six1. Genetic disruption of Six1 specifically in adult SCs impaired myogenic cell differentiation, impaired myofiber repair during regeneration, and perturbed homeostasis of the stem cell niche, as indicated by an increase in SC self-renewal. Six1 regulated the expression of the myogenic regulatory factors MyoD and Myogenin, but not Myf5, which suggests that Six1 acts on divergent genetic networks in the embryo and in the adult. Moreover, we demonstrate that Six1 regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway during regeneration via direct control of Dusp6 transcription. Muscles lacking Dusp6 were able to regenerate properly but showed a marked increase in SC number after regeneration. We conclude that Six1 homeoproteins act as a rheostat system to ensure proper regeneration of the tissue and replenishment of the stem cell pool during the events that follow skeletal muscle trauma.

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.


2020 ◽  
Vol 31 (16) ◽  
pp. 1703-1713
Author(s):  
Louise A. Moyle ◽  
Richard Y. Cheng ◽  
Haijiao Liu ◽  
Sadegh Davoudi ◽  
Silvia A. Ferreira ◽  
...  

The skeletal muscle stem cell niche transiently stiffens during the tissue repair process, which serves to increase planar-oriented divisions and, when combined with WNT7a, induces symmetric cell division to expand the stem cell pool.


Stem Cells ◽  
2021 ◽  
Vol 39 (6) ◽  
pp. 737-749
Author(s):  
Qi Liu ◽  
Su Pan ◽  
Shijie Liu ◽  
Sui Zhang ◽  
James T. Willerson ◽  
...  

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Shantisree Sandeepani Rayagiri ◽  
Daniele Ranaldi ◽  
Alexander Raven ◽  
Nur Izzah Farhana Mohamad Azhar ◽  
Olivier Lefebvre ◽  
...  

2016 ◽  
Vol 121 (5) ◽  
pp. 1053-1058 ◽  
Author(s):  
Koyal Garg ◽  
Marni D. Boppart

Skeletal muscle is endowed with a remarkable capacity for regeneration, primarily due to the reserve pool of muscle resident satellite cells. The satellite cell is the physiologically quiescent muscle stem cell that resides beneath the basal lamina and adjacent to the sarcolemma. The anatomic location of satellite cells is in close proximity to vasculature where they interact with other muscle resident stem/stromal cells (e.g., mesenchymal stem cells and pericytes) through paracrine mechanisms. This mini-review describes the components of the muscle stem cell niche, as well as the influence of exercise and aging on the muscle stem cell niche. Although exercise promotes ECM reorganization and stem cell accumulation, aging is associated with dense ECM deposition and loss of stem cell function resulting in reduced regenerative capacity and strength. An improved understanding of the niche elements will be valuable to inform the development of therapeutic interventions aimed at improving skeletal muscle regeneration and adaptation over the life span.


2013 ◽  
Vol 93 (1) ◽  
pp. 23-67 ◽  
Author(s):  
Hang Yin ◽  
Feodor Price ◽  
Michael A. Rudnicki

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.


2012 ◽  
Vol 2 (1) ◽  
pp. 11-21
Author(s):  
Silvia Cristini ◽  
Giulio Alessandri ◽  
Francesco Acerbi ◽  
Daniela Tavian ◽  
Eugenio A. Parati ◽  
...  

2012 ◽  
Vol 2 (1) ◽  
pp. 11-21
Author(s):  
Silvia Cristini ◽  
Giulio Alessandri ◽  
Francesco Acerbi ◽  
Daniela Tavian ◽  
Eugenio A. Parati ◽  
...  

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