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Levator Ani Satellite Cells (LASCs) treated with Nonsteroidal Androgen Receptor Agonist (NARA)

ABSTRACT: High regenerative capacity of adult skeletal muscle relies on a self-renewing depot of adult stem cells, termed muscle satellite cells (MSCs). A novel MSC line was isolated from the rat levator ani muscle and termed Levator Ani Satellite Cells (LASCs). Androgen, a known mediator of overall body composition and specifically skeletal muscle mass, has been shown to regulate MSCs. The use of non-steroidal androgen receptor agonists (NARA) aims to retain the beneficial influence of androgen on skeletal muscle, while circumventing undesirable cardiovascular and prostate-related side-effects. Primary objectives: 1) Identify biomarkers of satellite cell growth and differentiation, 2) Characterize a novel muscle satellite cell line, 3) Understand the effects of androgen (NARA) on rat satellite cell activation and recruitment.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE63489 | GEO | 2014/11/20

SECONDARY ACCESSION(S): PRJNA268026

REPOSITORIES: GEO

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Levator Ani Satellite Cells (LASCs) treated with Nonsteroidal Androgen Receptor Agonist (NARA)

Project description:High regenerative capacity of adult skeletal muscle relies on a self-renewing depot of adult stem cells, termed muscle satellite cells (MSCs). A novel MSC line was isolated from the rat levator ani muscle and termed Levator Ani Satellite Cells (LASCs). Androgen, a known mediator of overall body composition and specifically skeletal muscle mass, has been shown to regulate MSCs. The use of non-steroidal androgen receptor agonists (NARA) aims to retain the beneficial influence of androgen on skeletal muscle, while circumventing undesirable cardiovascular and prostate-related side-effects. Primary objectives: 1) Identify biomarkers of satellite cell growth and differentiation, 2) Characterize a novel muscle satellite cell line, 3) Understand the effects of androgen (NARA) on rat satellite cell activation and recruitment. LASCs will be treated with one of the following conditions (N=4 for all groups): 1) 0.2% DMSO, 4 hours; 2) 10 nM NARA, 4 hours; 3) 0.2% DMSO, 48 hours; 4) 10nM NARA, 48 hours

2014-11-20 | E-GEOD-63489 | biostudies-arrayexpress

Comparing gene expression between PICs and satellite cells from 1 week old muscle

Project description:The satellite cell is considered the major tissue-resident stem cell underlying muscle regeneration, however, multiple non-satellite cell myogenic progenitors have been identified. PW1/Peg3 is expressed in satellite cells as well as a subset of interstitial cells with myogenic potential termed PICs (PW1+ Interstitial Cells). PICs differ from satellite cells by their anatomical location (satellite cells are sublaminal and PICs are interstitial), they do not express any myogenic marker and arise from a Pax3-independent lineage. Upon isolation from juvenile muscle (1 to 3 weeks old), PICs are capable to form both skeletal and smooth muscle suggesting they constitute a more plastic population compared to satellite cells. We used microarrays to gain insight into the relantionship between PICs and satellite cells. PICs and satellite cells were isolated from 1-week old mouse muscle and subsequent RNA extraction was performed.

2012-09-01 | E-GEOD-40523 | biostudies-arrayexpress

Comparing gene expression between PICs and satellite cells from 1 week old muscle

2012-09-01 | GSE40523 | GEO

Gene profiling of quiescent and activated skeletal muscle satellite cells by an in vivo approach

Project description:The satellite cell of skeletal muscle provides a paradigm for quiescent and activated tissue stem cell states. We have carried out transcriptome analyses by comparing satellite cells from adult skeletal muscles, where they are mainly quiescent, with cells from growing muscles, regenerating (mdx) muscles, or with cells in culture, where they are activated. Our study gives new insights into the satellite cell biology during activation and in respect with its niche. We used microarrays to study the global programme of gene expression underlying adult satellite cell quiescence compared to activation states and to identify distinct classes of up-regulated genes in these two different states Skeletal muscle satellite cells were isolated by flow cytrometry using the GFP fluorescence marker from Pax3GFP/+ mice skeletal muscle. The transcriptome of quiescent satellite cells from adult Pax3GFP/+ muscle was compared to the transcriptome of activated satellite cells obtained from three different samples: 1) regenerating Pax3GFP/+:mdx/mdx muscle (Ad.mdx) , 2) growing 1 week old Pax3GFP/+ muscle (1wk), and 3) adult Pax3GFP/+ cells after 3 days in culture (Ad.cult).

2010-01-04 | E-GEOD-15155 | biostudies-arrayexpress

P38 signaling underlies a cell-autonomous loss of stem cell self-renewal in aged muscle

Project description:Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and decreased regenerative capacity, which can lead to sarcopenia and increased mortality. While the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Therefore, identification of signaling pathways affecting satellite cell function during aging may provide insights into therapeutic targets for combating sarcopenia. Here, we show that a cell-autonomous loss in self-renewal occurs via novel alterations in FGF and p38αβ MAPK signaling in old satellite cells. We further demonstrate that pharmacological manipulation of these pathways can ameliorate age-associated self-renewal defects. Thus, our data highlight an age-associated deregulation of a satellite cell homeostatic network and reveals potential therapeutic opportunities for the treatment of progressive muscle wasting. Satellite cells were isolated from young (3-6mo) and aged (20-25mo) adult mice; individual date files represent 2 independent pools of RNA from 4-8 mice at each timepoint.

2013-09-01 | E-GEOD-47104 | biostudies-arrayexpress

Direct reprogramming of mouse fibroblasts into functional skeletal muscle progenitors

Project description:Skeletal muscle harbors quiescent stem cells termed satellite cells and proliferative progenitors termed myoblasts, which play pivotal roles during muscle regeneration. However, current technology does not allow permanent capture of these cell populations in vitro. Here, we show that ectopic expression of the myogenic transcription factor MyoD, combined with exposure to small molecules, reprograms mouse fibroblasts into expandable induced myogenic progenitor cells (iMPCs). iMPCs express key skeletal muscle stem and progenitor cell markers including Pax7 and Myf5 and give rise to Dystrophin-expressing myofibers upon transplantation, a subset of which maintain Pax7 expression in vivo and sustain serial regenerative responses. Similar to satellite cells, iMPCs originate from Pax7+ cells and require Pax7 itself for maintenance. Finally, we show that iMPCs can be established from muscle tissue following small molecule exposure alone. This study thus reports on a robust approach to derive expandable myogenic stem/progenitor-like cells from multiple differentiated cell types.

2018-05-01 | GSE108543 | GEO

Direct reprogramming of mouse fibroblasts into functional skeletal muscle progenitors

2018-05-01 | GSE92336 | GEO

miR-206 modulates the pathogenesis of muscular dystrophy of mdx mice

Project description:In response to skeletal muscle injury, adult myogenic stem cells, known as satellite cells, are activated and undergo proliferation and differentiation to regenerate new muscle fibers. The skeletal muscle-specific microRNA, miR-206, is up-regulated in satellite cells following muscle injury, but its role in muscle regeneration has not been defined. Here we show that skeletal muscle regeneration in response to cardiotoxin injury is impaired in mice lacking miR-206. Loss of miR-206 also accelerates and exacerbates the dystrophic phenotype of mdx mice, a model for Duchenne muscular dystrophy. MiR-206 promotes satellite cell differentiation and fusion to form multinucleated myofibers by suppressing a collection of negative regulators of myogenesis. Our findings reveal an essential role for miR-206 in satellite cell differentiation during skeletal muscle regeneration and as a modulator of Duchenne muscular dystrophy. total RNA obtained from TA muscle of mdx and 3 miR-206 KO; mdx mice at 3 months of age.

2012-04-30 | E-GEOD-36077 | biostudies-arrayexpress

Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation [RNA-seq]

Project description:Satellite cells, the stem cells of skeletal muscle tissue, hold a remarkable regeneration capacity and therapeutic potential in regenerative medicine. However, low satellite cell yield from autologous or donor-derived muscles hinders the adoption of satellite cell transplantation for the treatment of muscle diseases, including Duchenne muscular dystrophy (DMD). To address this limitation, here we investigated whether satellite cells can be derived in allogeneic or xenogeneic animal hosts. First, injection of CRISPR/Cas9-corrected mouse DMD-induced pluripotent stem cells (iPSCs) into mouse blastocysts carrying an ablation system of host satellite cells gave rise to intraspecies chimeras exclusively carrying iPSC-derived satellite cells. Furthermore, injection of genetically corrected DMD-iPSCs into rat blastocysts resulted in the formation of interspecies rat-mouse chimeras harboring mouse satellite cells. Remarkably, iPSC-derived satellite cells or derivative myoblasts produced in intraspecies or interspecies chimeras restored dystrophin expression in DMD mice following intramuscular transplantation, and contributed to the satellite cell pool. Collectively, this study demonstrates the feasibility of producing therapeutically competent stem cells across divergent animal species, raising the possibility of generating human muscle stem cells in large animals for regenerative medicine purposes.

2024-04-25 | GSE215061 | GEO

Generation of allogenic and xenogeneic functional muscle stem cells for intramuscular transplantation [scRNA-seq]

2024-04-25 | GSE254371 | GEO

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