Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Restoration of CPEB4 Prevents Muscle Stem Cell Senescence during Aging

ABSTRACT: Muscle stem cells (MuSCs) are required for muscle regeneration. In resting muscles, MuSCs are kept in quiescence. After injury, MuSCs undergo rapid activation, proliferation and differentiation to repair damaged muscles. Age-associated impairments in stem cell functions correlate with a decline in somatic tissue regeneration capacity during aging. However, the mechanisms underlying the molecular regulation of adult stem cell aging remain elusive. Here, we obtained quisecent MuSCs from young, old, geriatric mice for high resolution mass spectrometry Bruker timsTOF Pro. By comparison of young proteome to old MuSCs proteome or geriatric MuSC proteome, we identified the pathways that are differentially during aging.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Muscle Stem Cell, Skeletal Muscle Satellite Cell

SUBMITTER: Wenxin ZHANG

LAB HEAD: Tom Hiu Tung CHEUNG

PROVIDER: PXD041614 | Pride | 2023-06-26

REPOSITORIES: pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	15M-1_1_1_1_0.mzid.gz	Mzid
	15M-1_2_1_1_0.mzid.gz	Mzid
	15M-1_Slot2-44_1_8595.d.zip	Other
	15M-1_Slot2-44_1_8595.mgf	Mgf
	15M-1_Slot2-44_2_8596.d.zip	Other

Items per page:

1 - 5 of 127

Similar Datasets

Mouse Muscle Stem Cell Proteome during Activation and CPEB1 Dependent Proteome in Mouse Muscle Stem Cell

Project description:Muscle Stem Cells or satellite cells (SCs) are required for muscle regeneration. In resting muscles, SCs are kept in quiescence. After injury, SCs undergo rapid activation, proliferation and differentiation to repair damaged muscles. The transcriptome alteration during SC activation is well characterized. While transcriptome is not exactly represent proteome because of post-transcriptional regulations such as miRNA induced gene silencing. However, little is known about SC proteome. We obtained quisecent SCs (QSCs) and freshly isolated SCs (fiSCs, early activated SCs) and activated SCs (ASCs) for high resolution mass spectrometry Bruker timsTOF Pro. Thus, we uncovered the QSC proteome. By comparison of QSC proteome to fiuSCs proteome or ASCs proteome, we identified the pathways that are differentially expressed between them. Forthermore, we characterized a translational regulator CPEB1 reprogrammed translation landscape for SC activation.

2021-11-05 | PXD018865 | Pride

Deep proteome of aging skeletal muscles reveals Smoc2 as a modulator of satellite cell regenerative capacity

Project description:During aging, the number and functionality of muscle stem cells (MuSCs) decreases leading to impaired regeneration of aged skeletal muscle. In addition to intrinsic changes in aged MuSCs, extracellular matrix (ECM) proteins deriving from other cell types, e.g., fibrogenic-adipogenic progenitor cells (FAPs), contribute to the aging phenotype of MuSCs and impaired regeneration in the elderly. So far, no comprehensive analysis on how age-dependent changes in the whole skeletal muscle proteome affect MuSC function have been conducted. Here, we investigated age-dependent changes in the proteome of different skeletal muscle types by applying deep quantitative mass spectrometry. We identified 183 extracellular matrix proteins that show different abundances in skeletal muscles of old mice. By integrating single cell sequencing data, we reveal that transcripts of those ECM proteins are mainly expressed in FAPs, suggesting that FAPs are the main contributors to ECM remodelling during aging. We functionally investigated one of those ECM molecules, namely Smoc2, which is aberrantly expressed during aging. We show that Smoc2 levels are elevated during regeneration and that its accumulation in the aged MuSC niche causes impairment of MuSCs function through constant activation of integrin/MAPK signaling. In vivo, supplementation of exogenous Smoc2 hampers the regeneration of young muscles following serial injuries, leading to a phenotype reminiscent of regenerating aged skeletal muscle. Taken together, we provide a comprehensive resource of changes in the composition of the ECM of aged skeletal muscles, we pinpoint the cell types driving these changes, and we identify a new niche protein causing functional impairment of MuSCs thereby hampering the regeneration capacity of skeletal muscles.

2021-11-25 | PXD015728 | Pride

Deep proteome of aging skeletal muscles reveals Smoc2 as a modulator of satellite cell regenerative capacity

2021-11-25 | PXD015616 | Pride

Changes of the muscle stem cell niche during aging

Project description:During aging, the regenerative capacity of skeletal muscle decreases due to intrinsic changes in muscle stem cells (MuSCs) and alterations in their niche. Here, we used quantitative mass spectrometry to characterize intrinsic changes in the MuSC proteome and remodeling of the MuSC niche during aging. We generated a network connecting age-affected ligands located in the niche and cell surface receptors on MuSCs. Thereby, we revealed signaling via Integrins, Lrp1, Egfr and Cd44 as the major cell communication axes perturbed through aging. We investigated the effect of Smoc2, a secreted protein that accumulates with aging, originating from fibro-adipogenic progenitors. Increased levels of Smoc2 contribute to the aberrant Itgb1/MAPK signaling observed during aging, thereby causing impaired MuSC functionality and muscle regeneration. By connecting changes in the proteome of MuSCs to alterations of their niche, our work will enable a better understanding of how MuSCs are affected during aging.

2021-11-10 | PXD023628 | Pride

mouse stem cell SWATH-MS

Project description:Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to SC senescence during aging. Here we demonstrate the importance of cellular NAD+ level and its impact on mitochondrial activity as a pivotal switch to modulate muscle stem cell (MuSC) senescence. Importantly, the induction of the mitochondrial unfolded protein response (UPRmt) and of prohibitin proteins, subsequent to increasing cellular NAD+ with the precursor nicotinamide riboside (NR), rejuvenates MuSCs in aged mice. NR also prevents MuSCs senescence in Mdx mice, a mouse model of muscular dystrophy. Extending these observations to other SC pools and on the organism as a whole, we demonstrate that NR delays neural stem cell (NSC) and melanocyte stem cell (McSC) senescence, while also increasing mouse lifespan. Strategies that conserve cellular NAD+ could therefore be utilized to reprogram dysfunctional SCs in aging and disease to improve lifespan in mammals

2022-02-22 | PXD003865 | Pride

Aptamer-conjugated gold nanoparticles enable selective oligonucleotide delivery into muscle 2 stem cells to promote regeneration of dystrophic muscles

Project description:Inefficient targeting of muscle stem cells (MuSCs) represents a major bottleneck of current 27 therapeutic strategies for muscular dystrophies, as it precludes the possibility to promote 28 compensatory regeneration. Here we describe a novel delivery platform, based on gold nanoparticles, 29 that enables the release of therapeutic oligonucleotides into MuSCs. We demonstrate that AuNPs 30 conjugation to an aptamer against integrin directs either local or systemic delivery of 31 microRNA-206 to MuSCs, thereby promoting muscle regeneration in a mouse model of Duchenne 32 Muscular Dystrophy. We show here that this platform is biocompatible, non-toxic, non33 immunogenic, and adaptable for release of a wide range of therapeutic oligonucleotides into diseased 34 muscles.

2024-11-11 | PXD049295 | Pride

Overloading MuSCs

Project description:Skeletal muscle possesses the ability to adapt its size in response to milieus, which is called plasticity. Overload like resistance training induces the increment of muscle mass called muscle hypertrophy. Muscle stem cells (also known as muscle stem cells) function to supply new nuclei for myofiber during the overload in muscle. Using compensatory hypertrophy in plantaris muscles, we isolated MuSCs from plantaris muscles 4 days after surgery. Control MuSCs were also prepared from sham plantaris muscles.

2019-09-23 | GSE135903 | GEO

Changes of the muscle stem cell niche during aging

2021-11-10 | PXD023643 | Pride

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

Project description: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.

2020-09-30 | GSE154813 | GEO

Sex hormones control muscle stem cells

Project description:Quiescent adult muscle stem cells (MuSCs) regenerate skeletal muscle upon injury throughout life. However, aged skeletal muscles fail to maintain stem cell quiescence, leading to declines in MuSC number and functionality. Although autophagy plays an important role in the maintenance of MuSC quiescence, how quiescent MuSCs and their autophagy levels are maintained throughout life is largely unknown. The current study reveals how GnRH, a hypothalamic hormone, maintains the quiescence of adult MuSCs by preventing the onset of senescence and how the decline of sex steroids in organismal ageing is implicated in MuSC ageing.

2019-10-05 | GSE121016 | GEO