Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Muscle satellite cell specific proteasome deficient mice

ABSTRACT: Adult muscle stem cells (satellite cells) are required for adult skeletal muscle regeneration. A proper balance between quiescence, proliferation, and differentiation is essential for the maintenance of the satellite cell pool and their regenerative function. Although the ubiquitin-proteasome is required for most protein degradation in mammalian cells, how its dysfunction affects tissue stem cells remains unclear. Here, we investigated the function of the proteasome in satellite cells using mice lacking the crucial proteasomal component, Rpt3. Ablation of Rpt3 in satellite cells decreased proteasome activity. Proteasome dysfunction in Rpt3-deficient satellite cells impaired their ability to proliferate, survive and differentiate, resulting in defective muscle regeneration. We found that inactivation of proteasomal activity induced proliferation defects and apoptosis in satellite cells. Mechanistically, insufficient proteasomal activity upregulated the p53 pathway, which caused cell-cycle arrest. Our findings delineate a critical function of the proteasome system in maintaining satellite cells in adult muscle.

ORGANISM(S): Mus musculus

PROVIDER: GSE114354 | GEO | 2018/10/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Muscle specific proteasome deficient mice

Project description:The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes for protein and organelle clearance. In skeletal muscle, both systems’ excessive activation induces severe muscle loss. Although altered proteasomal function has been observed in various myopathies, the specific role of proteasomal activity in skeletal muscle has not been determined by loss-of-function approaches. Here, we report that muscle-specific deletion of a crucial proteasomal gene, Rpt3, resulted in profound muscle atrophy and decrease in force. Rpt3 null muscles showed reduced proteasomal activity in early age, accumulation of basophilic structure, disorganization of sarcomere, and formation of vacuoles and concentric membranous structures in electronmicroscope. We also observed accumulation of ubiquitin, p62, LC3, TDP43, FUS and VCP proteins. Proteasomal activity is important to preserve muscle mass and to maintain myofiber integrity. Our results suggest that inhibition/alteration of proteasomal activity can contribute to myofiber degeneration and weakness in muscle disorders, such as inclusion body myositis, characterized by accumulation of abnormal inclusions. Tibialis anterior muscles from Rpt3 null and control mice. each 3 mice.

2014-09-30 | E-GEOD-34896 | biostudies-arrayexpress

Islr regulates satellite cells asymmetric division through Sparc/p-ERK1/2 signaling pathway

Project description:Satellite cells are adult muscle stem cells responsible for muscle regeneration after acute or chronic injuries. The balance between stem cell self-renewal and differentiation impacts the kinetics and efficiency of skeletal muscle regeneration. This study elucidated the function of Islr in satellite cell asymmetric division. Satellite cell specific deletion of Islr compromises muscle regeneration in adult mice by impairing the satellite cell pool. Islr is pivotal for satellite cell proliferation and its deletion promotes asymmetric cell fate segregation of satellite cells. A mechanistic search revealed that Islr interacts and stabilizes the Sparc protein, which activates p-ERK1/2 signaling required for asymmetric division. In combination, the findings have identified Islr as a key regulator of satellite cell asymmetric division through the Sparc/p-ERK1/2 signaling pathway, which provides a new insight into satellite cell biology and open avenues for the treatment of myopathy.

2023-08-16 | GSE210951 | GEO

Muscle specific proteasome deficient mice

2014-09-30 | GSE34896 | GEO

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

Geriatric muscle stem cells switch reversible quiescence into senescence (Set 3; Adult vs. Young)

Project description:Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with aging. We report that geriatric satellite cells, compared to old and adult cells, are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and this irreversibly affects their intrinsic regenerative and self-renewal capacities. We analyzed the global changes in gene expression occurring within muscle stem cells (satellite cells) in homeostatic conditions during physiological aging. Pure satellite cell populations from dissociated skeletal muscle from Young (2-3 months) and Adult (6 months) mice were isolated using a well-established flow cytometry protocol gating on integrin a7(+)/CD34(+) (positive selection) and Lin- (CD31, CD45, CD11b, Sca1) (negative selection).

2013-12-31 | E-GEOD-53726 | biostudies-arrayexpress

WT and AUF1 KO satellite cell RNA-sequencing

Project description:Following skeletal muscle injury, muscle stem cells (satellite cells) are activated, proliferate, and differentiate to form myofibers. We show that mRNA decay protein AUF1 regulates satellite cell function through targeted degradation of specific mRNAs. AUF1 targets certain mRNAs containing 3 AU-rich elements (AREs) for rapid decay. Auf1-/- (KO) mice undergo accelerated skeletal muscle wasting with age and impaired muscle repair following injury. Satellite cell mRNA analysis and regeneration studies demonstrate that auf1-/- satellite cell self-renewal is impaired due to increased stability and overexpression of ARE-mRNAs. Control of ARE-mRNA decay by AUF1 and potentially other ARE-binding proteins represents a mechanism for adult stem cell regulation and is implicated in human muscle wasting diseases. We report the RNA transcript expression profiles from sorted satellite cells isolated from wild type (WT) and AUF1-null (KO) mice hindlimb muscles Examination of RNA transcript expression from satellite cells of two genotypes Please note that mice are bred through a C57BL/6 strain of 129 background.

2016-07-21 | E-GEOD-83555 | biostudies-arrayexpress

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

Transcription factor Runx1 cooperates with MyoD and c-Jun to regulate the balance of myoblast proliferation/differentiation [Expression Study]

Project description:Runx1 is expressed in regenrating muscle, specifically in the muscle adult stem cells- the satellite cells. Its exact role and target genes were yet to be identified This experiment aimed at determining the Runx1 regulated genes in muscle regeneration, specifically in Satellite cells To elucidate the Runx1-mediated transcriptional program involved in early stages of muscle regeneration, we compared gene expression profiles in WT and Runx1f/f primary myobalsts (PM). PM were purified from both genotypes , Total RNA was isolated, reverse-transcribed, fragmented, labeled and hybridized to Affymetrix MoGene 1.0 ST DNA array.

2015-07-23 | E-GEOD-55556 | biostudies-arrayexpress

Expression data from skeletal muscle satellite cells at different development stages

Project description:Satellite cells are responsible for the long-term regenerative capacity of adult skeletal muscle. The diminished muscle performance and regenerative capacity of aged muscle is thought to reflect progressive fibrosis and atrophy. Whether this reduction in muscle competency also involves a diminishment in the intrinsic regulation of satellite cell self-renewal remains unknown. We used microarray to identify gene expression changes underlying the marked reduction in the capacity of satellite cells to self-renew, contribute to regeneration and repopulate the niche as they age. Skeletal muscles from heterozygous Pax7-ZsGreen mice were isolated at defined stages: E17.5 (fetal - whole forelimb and hindlimb), postnatal day 21 (adolescent - hindlimb), 2-3 month old (young adult - hindlimb) and >1 year old (older adult - hindlimb) mice. ZsGreen-positive skeletal muscle satellite cells were isolated by FACS and pooled (fetal n=4, adolescent n=6, young adult n=8 and older adult n=8 mice).

2014-05-26 | E-GEOD-47401 | biostudies-arrayexpress

Identifying signals from the skeletal muscle niche that regulate satellite cell function

Project description:Skeletal muscle is the most common tissue in the body. Its continued maintenance and regeneration throughout life is essential to the function of the organism. Satellite cells are critical to regeneration of the skeletal muscle and strategies to improve function of satellite cells are of great importance. Muscle-resident Fibro-Adipogenic Precursors (FAPs) cells are a critical component of the satellite cell niche and help orchestrate efficient muscle regeneration and potentiate satellite cell differentiation via soluble or secreted factors. Populations with similar phenotype and function to muscle FAPs have been isolated from the skin and white adipose tissue. Interactions between tissue-specific FAP cells and resident stem cells in those tissues might be conserved. Therefore, defining specific factors that mediate the relationship between muscle FAPs and satellite cells would have implications for other organs.

2019-06-30 | GSE67117 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data