Role of satellite cells in growth and regeneration of skeletal muscles

Postnatal growth and regeneration capacity of skeletal muscles is dependent mainly on adult muscle stem cells called satellite cells. Satellite cells are quiescent mononucleated cells that are normally located outside the sarcolemma within the basal lamina of the muscle fiber. Their activation, which results from injury, is manifested by mobilization, proliferation, differentiation and, ultimately, fusion into new muscle fibers. The satellite cell pool is responsible for the remarkable regenerative capacity of skeletal muscles. Moreover, these cells are capable of self-renewal and can give rise to myogenic progeny.

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Transcriptome and epigenome diversity and plasticity of muscle stem cells following transplantation

10.1101/2020.05.20.107219 ◽

2020 ◽

Author(s):

Brendan Evano ◽

Diljeet Gill ◽

Irene Hernando-Herraez ◽

Glenda Comai ◽

Thomas M. Stubbs ◽

...

Keyword(s):

Stem Cells ◽

Skeletal Muscles ◽

Molecular Diversity ◽

Anatomical Location ◽

Limb Muscle ◽

Regenerative Capacity ◽

Self Renewal ◽

Site Specific ◽

Muscle Stem Cells ◽

Molecular Determinants

ABSTRACTAdult skeletal muscles are maintained during homeostasis and regenerated upon injury by muscle stem cells (MuSCs). A heterogeneity in self-renewal, differentiation and regeneration properties has been reported for MuSCs based on their anatomical location. Although MuSCs derived from extraocular muscles (EOM) have a higher regenerative capacity than those derived from limb muscles, the molecular determinants that govern these differences remain undefined. Here we show that EOM and limb MuSCs have distinct DNA methylation signatures associated with enhancers of location-specific genes, and that the EOM transcriptome is reprogrammed following transplantation into a limb muscle environment. Notably, EOM MuSCs expressed host-site specific positional Hox codes after engraftment and self-renewal within the host muscle. However, about 10% of EOM-specific genes showed engraftment-resistant expression, pointing to cell-intrinsic molecular determinants of the higher engraftment potential of EOM MuSCs. Our results underscore the molecular diversity of distinct MuSC populations and molecularly define their plasticity in response to microenvironmental cues. These findings provide insights into strategies designed to improve the functional capacity of MuSCs in the context of regenerative medicine.

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Transcriptome and epigenome diversity and plasticity of muscle stem cells following transplantation

PLoS Genetics ◽

10.1371/journal.pgen.1009022 ◽

2020 ◽

Vol 16 (10) ◽

pp. e1009022

Author(s):

Brendan Evano ◽

Diljeet Gill ◽

Irene Hernando-Herraez ◽

Glenda Comai ◽

Thomas M. Stubbs ◽

...

Keyword(s):

Stem Cells ◽

Skeletal Muscles ◽

Molecular Diversity ◽

Anatomical Location ◽

Limb Muscle ◽

Regenerative Capacity ◽

Self Renewal ◽

Site Specific ◽

Muscle Stem Cells ◽

Molecular Determinants

Adult skeletal muscles are maintained during homeostasis and regenerated upon injury by muscle stem cells (MuSCs). A heterogeneity in self-renewal, differentiation and regeneration properties has been reported for MuSCs based on their anatomical location. Although MuSCs derived from extraocular muscles (EOM) have a higher regenerative capacity than those derived from limb muscles, the molecular determinants that govern these differences remain undefined. Here we show that EOM and limb MuSCs have distinct DNA methylation signatures associated with enhancers of location-specific genes, and that the EOM transcriptome is reprogrammed following transplantation into a limb muscle environment. Notably, EOM MuSCs expressed host-site specific positional Hox codes after engraftment and self-renewal within the host muscle. However, about 10% of EOM-specific genes showed engraftment-resistant expression, pointing to cell-intrinsic molecular determinants of the higher engraftment potential of EOM MuSCs. Our results underscore the molecular diversity of distinct MuSC populations and molecularly define their plasticity in response to microenvironmental cues. These findings provide insights into strategies designed to improve the functional capacity of MuSCs in the context of regenerative medicine.

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Loss of myogenic potential and fusion capacity of muscle stem cells isolated from contractured muscle in children with cerebral palsy

AJP Cell Physiology ◽

10.1152/ajpcell.00351.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. C247-C257 ◽

Cited By ~ 7

Author(s):

Andrea A. Domenighetti ◽

Margie A. Mathewson ◽

Rajeswari Pichika ◽

Lydia A. Sibley ◽

Leyna Zhao ◽

...

Keyword(s):

Dna Methylation ◽

Stem Cells ◽

Cerebral Palsy ◽

Satellite Cell ◽

Satellite Cells ◽

Skeletal Muscles ◽

Muscle Stem Cells ◽

Myogenic Potential ◽

Myotube Formation ◽

The Brain

Cerebral palsy (CP) is the most common cause of pediatric neurodevelopmental and physical disability in the United States. It is defined as a group of motor disorders caused by a nonprogressive perinatal insult to the brain. Although the brain lesion is nonprogressive, there is a progressive, lifelong impact on skeletal muscles, which are shorter, spastic, and may develop debilitating contractures. Satellite cells are resident muscle stem cells that are indispensable for postnatal growth and regeneration of skeletal muscles. Here we measured the myogenic potential of satellite cells isolated from contractured muscles in children with CP. When compared with typically developing (TD) children, satellite cell-derived myoblasts from CP differentiated more slowly (slope: 0.013 (SD 0.013) CP vs. 0.091 (SD 0.024) TD over 24 h, P < 0.001) and fused less (fusion index: 21.3 (SD 8.6) CP vs. 81.3 (SD 7.7) TD after 48 h, P < 0.001) after exposure to low-serum conditions that stimulated myotube formation. This impairment was associated with downregulation of several markers important for myoblast fusion and myotube formation, including DNA methylation-dependent inhibition of promyogenic integrin-β 1D (ITGB1D) protein expression levels (−50% at 42 h), and ~25% loss of integrin-mediated focal adhesion kinase phosphorylation. The cytidine analog 5-Azacytidine (5-AZA), a demethylating agent, restored ITGB1D levels and promoted myogenesis in CP cultures. Our data demonstrate that muscle contractures in CP are associated with loss of satellite cell myogenic potential that is dependent on DNA methylation patterns affecting expression of genetic programs associated with muscle stem cell differentiation and muscle fiber formation.

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Mitochondria in the maintenance of hematopoietic stem cells: new perspectives and opportunities

Blood ◽

10.1182/blood-2018-10-808873 ◽

2019 ◽

Vol 133 (18) ◽

pp. 1943-1952 ◽

Cited By ~ 16

Author(s):

Marie-Dominique Filippi ◽

Saghi Ghaffari

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Blood Cells ◽

Self Renewal ◽

Hematopoietic Stem ◽

Hematopoietic System ◽

Cellular Energy ◽

Cell Pool ◽

Stem Cell Pool

Abstract The hematopoietic system produces new blood cells throughout life. Mature blood cells all derived from a pool of rare long-lived hematopoietic stem cells (HSCs) that are mostly quiescent but occasionally divide and self-renew to maintain the stem cell pool and to insure the continuous replenishment of blood cells. Mitochondria have recently emerged as critical not only for HSC differentiation and commitment but also for HSC homeostasis. Mitochondria are dynamic organelles that orchestrate a number of fundamental metabolic and signaling processes, producing most of the cellular energy via oxidative phosphorylation. HSCs have a relatively high amount of mitochondria that are mostly inactive. Here, we review recent advances in our understanding of the role of mitochondria in HSC homeostasis and discuss, among other topics, how mitochondrial dynamism and quality control might be implicated in HSC fate, self-renewal, and regenerative potential.

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Oscillations of Delta-like1 regulate the balance between differentiation and maintenance of muscle stem cells

Nature Communications ◽

10.1038/s41467-021-21631-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yao Zhang ◽

Ines Lahmann ◽

Katharina Baum ◽

Hiromi Shimojo ◽

Philippos Mourikis ◽

...

Keyword(s):

Stem Cells ◽

Muscle Growth ◽

Regulatory Factor ◽

Self Renewal ◽

Muscle Stem Cells ◽

Cell Pool ◽

Cellular Source ◽

Skeletal Muscle Stem Cells ◽

Notch Ligands ◽

Stem Cell Pool

AbstractCell-cell interactions mediated by Notch are critical for the maintenance of skeletal muscle stem cells. However, dynamics, cellular source and identity of functional Notch ligands during expansion of the stem cell pool in muscle growth and regeneration remain poorly characterized. Here we demonstrate that oscillating Delta-like 1 (Dll1) produced by myogenic cells is an indispensable Notch ligand for self-renewal of muscle stem cells in mice. Dll1 expression is controlled by the Notch target Hes1 and the muscle regulatory factor MyoD. Consistent with our mathematical model, our experimental analyses show that Hes1 acts as the oscillatory pacemaker, whereas MyoD regulates robust Dll1 expression. Interfering with Dll1 oscillations without changing its overall expression level impairs self-renewal, resulting in premature differentiation of muscle stem cells during muscle growth and regeneration. We conclude that the oscillatory Dll1 input into Notch signaling ensures the equilibrium between self-renewal and differentiation in myogenic cell communities.

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Antioxidant Levels Represent a Major Determinant in the Regenerative Capacity of Muscle Stem Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e08-03-0274 ◽

2009 ◽

Vol 20 (1) ◽

pp. 509-520 ◽

Cited By ~ 65

Author(s):

Kenneth L. Urish ◽

Joseph B. Vella ◽

Masaho Okada ◽

Bridget M. Deasy ◽

Kimimasa Tobita ◽

...

Keyword(s):

Stem Cells ◽

Antioxidant Capacity ◽

Functional Characteristic ◽

Post Transplantation ◽

Regenerative Capacity ◽

Inflammatory Stress ◽

Muscle Stem Cells ◽

Cardiac Muscles

Stem cells are classically defined by their multipotent, long-term proliferation, and self-renewal capabilities. Here, we show that increased antioxidant capacity represents an additional functional characteristic of muscle-derived stem cells (MDSCs). Seeking to understand the superior regenerative capacity of MDSCs compared with myoblasts in cardiac and skeletal muscle transplantation, our group hypothesized that survival of the oxidative and inflammatory stress inherent to transplantation may play an important role. Evidence of increased enzymatic and nonenzymatic antioxidant capacity of MDSCs were observed in terms of higher levels of superoxide dismutase and glutathione, which appears to confer a differentiation and survival advantage. Further when glutathione levels of the MDSCs are lowered to that of myoblasts, the transplantation advantage of MDSCs over myoblasts is lost when transplanted into both skeletal and cardiac muscles. These findings elucidate an important cause for the superior regenerative capacity of MDSCs, and provide functional evidence for the emerging role of antioxidant capacity as a critical property for MDSC survival post-transplantation.

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