Faculty Opinions recommendation of Glucose Metabolism Drives Histone Acetylation Landscape Transitions that Dictate Muscle Stem Cell Function.

Duchenne muscular dystrophy (DMD) is a devastating and debilitating muscle degenerative disease affecting 1 in every 3,500 male births worldwide. DMD is progressive and fatal; accumulated weakening of the muscle tissue leads to an inability to walk and eventual loss of life due to respiratory and cardiac failure. Importantly, there remains no effective cure for DMD. DMD is caused by defective expression of the <i>DMD</i> gene, which encodes for dystrophin, a component of the dystrophin glycoprotein complex. In muscle fibers, this protein complex plays a critical role in maintaining muscle membrane integrity. Emerging studies have shown that muscle stem cells, which are adult stem cells responsible for muscle repair, are also affected in DMD. DMD muscle stem cells do not function as healthy muscle stem cells, and their impairment contributes to disease progression. Deficiencies in muscle stem cell function include impaired establishment of cell polarity leading to defective asymmetric stem cell division, reduced myogenic commitment, impaired differentiation, altered metabolism, and enhanced entry into senescence. Altogether, these findings indicate that DMD muscle stem cells are dysfunctional and have impaired regenerative potential. Although recent advances in adeno-associated vector and antisense oligonucleotide-mediated mechanisms for gene therapy have shown clinical promise, the current therapeutic strategies for muscular dystrophy do not effectively target muscle stem cells and do not address the deficiencies in muscle stem cell function. Here, we discuss the merits of restoring endogenous muscle stem cell function in degenerating muscle as a viable regenerative medicine strategy to mitigate DMD.

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Rejuvenating Muscle Stem Cell Function: Restoring Quiescence and Overcoming Senescence

Rejuvenation Research ◽

10.1089/rej.2016.1829 ◽

2016 ◽

Vol 19 (2) ◽

pp. 182-186 ◽

Cited By ~ 8

Author(s):

Andrew R. Mendelsohn ◽

James W. Larrick

Keyword(s):

Stem Cell ◽

Cell Function ◽

Muscle Stem Cell

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Arsenic Promotes NF-Κb-Mediated Fibroblast Dysfunction and Matrix Remodeling to Impair Muscle Stem Cell Function

Stem Cells ◽

10.1002/stem.2232 ◽

2016 ◽

Vol 34 (3) ◽

pp. 732-742 ◽

Cited By ~ 9

Author(s):

Changqing Zhang ◽

Ricardo Ferrari ◽

Kevin Beezhold ◽

Kristen Stearns-Reider ◽

Antonio D'Amore ◽

...

Keyword(s):

Stem Cell ◽

Cell Function ◽

Matrix Remodeling ◽

Muscle Stem Cell

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Engineered Heterochronic Parabiosis in 3D Microphysiological System for Identification of Muscle Rejuvenating Factors

10.1101/2020.03.10.975482 ◽

2020 ◽

Author(s):

Yunki Lee ◽

Jeongmoon J. Choi ◽

Song Ih Ahn ◽

Nan Hee Leea ◽

Woojin M. Han ◽

...

Keyword(s):

Stem Cell ◽

Cell Function ◽

Three Dimensional ◽

Muscle Stem Cell ◽

Organ Systems ◽

Systemic Factors ◽

Underlying Mechanisms ◽

On Chip

AbstractExposure of aged mice to a young systemic milieu revealed remarkable rejuvenation effects on aged tissues, including skeletal muscle. Although some candidate factors have been identified, the exact identity and the underlying mechanisms of putative rejuvenating factors remain elusive, mainly due to the complexity of in vivo parabiosis. Here, we present an in vitro muscle parabiosis system that integrates young- and old-muscle stem cell vascular niche on a three-dimensional microfluidic platform designed to recapitulate key features of native muscle stem cell microenvironment. This innovative system enables mechanistic studies of cellular dynamics and molecular interactions within the muscle stem cell niche, especially in response to conditional extrinsic stimuli of local and systemic factors. We demonstrate that vascular endothelial growth factor (VEGF) signaling from endothelial cells and myotubes synergistically contribute to the rejuvenation of the aged muscle stem cell function. Moreover, with the adjustable on-chip system, we can mimic both blood transfusion and parabiosis and detect the time-varying effects of anti-geronic and pro-geronic factors in a single organ or multi-organ systems. Our unique approach presents a complementary in vitro model to supplement in vivo parabiosis for identifying potential anti-geronic factors responsible for revitalizing aging organs.

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Molecular Regulation and Rejuvenation of Muscle Stem (Satellite) Cell Aging

The Indonesian Biomedical Journal ◽

10.18585/inabj.v7i2.73 ◽

2015 ◽

Vol 7 (2) ◽

pp. 73

Author(s):

Anna Meiliana ◽

Nurrani Mustika Dewi ◽

Andi Wijaya

Keyword(s):

Skeletal Muscle ◽

Stem Cells ◽

Stem Cell ◽

Satellite Cell ◽

Muscle Mass ◽

Satellite Cells ◽

Cell Function ◽

Muscle Stem Cell ◽

Muscle Aging ◽

Age Related

BACKGROUND: Age-related muscle loss leads to lack of muscle strength, resulting in reduced posture and mobility and an increased risk of falls, all of which contribute to a decrease in quality of life. Skeletal muscle regeneration is a complex process, which is not yet completely understood.CONTENT: Skeletal muscle undergoes a progressive age-related loss in mass and function. Preservation of muscle mass depends in part on satellite cells, the resident stem cells of skeletal muscle. Reduced satellite cell function may contribute to the age-associated decrease in muscle mass. Recent studies have delineated that the aging process in organ stem cells is largely caused by age-specific changes in the differentiated niches, and that regenerative outcomes often depend on the age of the niche, rather than on stem cell age. It is likely that epigenetic states will be better define such key satellite cell features as prolonged quiescence and lineage fidelity. It is also likely that DNA and histone modifications will underlie many of the changes in aged satellite cells that account for age-related declines in functionality and rejuvenation through exposure to the systemic environment.SUMMARY: Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and regenerative capacity, which can lead to sarcopenia and increased mortality. Although the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Decreased muscle stem cell function in aging has long been shown to depend on altered environmental cues, whereas the contribution of intrinsic mechanisms remained less clear. Signals in the aged niche were shown to cause permanent defects in the ability of satellite cells to return to quiescence, ultimately also impairing the maintenance of self-renewing satellite cells. Therefore, only anti-aging strategies taking both factors, the stem cell niche and the stem cells per se, into consideration may ultimately be successful.KEYWORDS: satellite cell, muscle, aging, niche, regenerations

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Aging Disrupts Muscle Stem Cell Function by Impairing Matricellular WISP1 Secretion from Fibro-Adipogenic Progenitors

Cell Stem Cell ◽

10.1016/j.stem.2018.12.014 ◽

2019 ◽

Vol 24 (3) ◽

pp. 433-446.e7 ◽

Cited By ~ 39

Author(s):

Laura Lukjanenko ◽

Sonia Karaz ◽

Pascal Stuelsatz ◽

Uxia Gurriaran-Rodriguez ◽

Joris Michaud ◽

...

Keyword(s):

Stem Cell ◽

Cell Function ◽

Muscle Stem Cell

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Cytokine Mediated Control of Muscle Stem Cell Function

Growth Factors and Cytokines in Skeletal Muscle Development, Growth, Regeneration and Disease - Advances in Experimental Medicine and Biology ◽

10.1007/978-3-319-27511-6_2 ◽

2016 ◽

pp. 27-44 ◽

Cited By ~ 10

Author(s):

Sophie Joanisse ◽

Gianni Parise

Keyword(s):

Stem Cell ◽

Cell Function ◽

Muscle Stem Cell

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Regulation of muscle stem cell function

10.1016/bs.vh.2021.02.012 ◽

2021 ◽

Author(s):

Julia von Maltzahn

Keyword(s):

Stem Cell ◽

Cell Function ◽

Muscle Stem Cell

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Age and prior exercise in vivo determine the subsequent in vitro molecular profile of myoblasts and nonmyogenic cells derived from human skeletal muscle

AJP Cell Physiology ◽

10.1152/ajpcell.00049.2019 ◽

2019 ◽

Vol 316 (6) ◽

pp. C898-C912 ◽

Cited By ~ 7

Author(s):

Cecilie J. L. Bechshøft ◽

Simon M. Jensen ◽

Peter Schjerling ◽

Jesper L. Andersen ◽

Rene B. Svensson ◽

...

Keyword(s):

Skeletal Muscle ◽

Stem Cell ◽

Human Skeletal Muscle ◽

Cell Function ◽

Myogenic Differentiation ◽

Molecular Profile ◽

Muscle Stem Cell ◽

Myogenic Cells

The decline in skeletal muscle regenerative capacity with age is partly attributed to muscle stem cell (satellite cell) dysfunction. Recent evidence has pointed to a strong interaction between myoblasts and fibroblasts, but the influence of age on this interaction is unknown. Additionally, while the native tissue environment is known to determine the properties of myogenic cells in vitro, how the aging process alters this cell memory has not been established at the molecular level. We recruited 12 young and 12 elderly women, who performed a single bout of heavy resistance exercise with the knee extensor muscles of one leg. Five days later, muscle biopsies were collected from both legs, and myogenic cells and nonmyogenic cells were isolated for in vitro experiments with mixed or separated cells and analyzed by immunostaining and RT-PCR. A lower myogenic fusion index was detected in the cells from the old versus young women, in association with differences in gene expression levels of key myogenic regulatory factors and senescence, which were further altered by performing exercise before tissue sampling. Coculture with nonmyogenic cells from the elderly led to a higher myogenic differentiation index compared with nonmyogenic cells from the young. These findings show that the in vitro phenotype and molecular profile of human skeletal muscle myoblasts and fibroblasts is determined by the age and exercise state of the original in vivo environment and help explain how exercise can enhance muscle stem cell function in old age.

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