Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Whole genome bisulfite sequencing of young and old satellite cells

ABSTRACT: The function of skeletal muscle stem cells (MuSC) declines during aging, contributing to the advent of age-related myopathies. However, whether this decline is the result of accumulating cellular damage, altered heterogeneity in stem cell populations or due to the effect of the changing niche environment remains largely unknown. By scRNA-Seq, we show that the age-related reduction in the MuSC pool is not stochastic, with different subpopulations being distinctly affected in aging. Using an in vivo allogeneic stem cell transplantation model, we show that exposure of MuSCs from old mice to a youthful niche environment significantly restores the gene expression of genes that are altered in aging. We show that age-related changes in the MuSC transcriptome are mainly driven by alterations in chromatin and transcription but are not due to posttranscriptional mechanisms affecting RNA stability. Furthermore, our data indicates that the portion of the genome that is activated in aging is significantly more responsive to restoration by niche factors compared to the repressed counterpart. Taken together, our data reveals that the niche environment plays a decisive role in controlling the transcriptional activity of MuSCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE171604 | GEO | 2023/01/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

RNA-Sequencing of young and aged satellite cells before and after transplantation into the young niche

Project description:The function of skeletal muscle stem cells (MuSC) declines during aging, contributing to the advent of age-related myopathies. However, whether this decline is the result of accumulating cellular damage, altered heterogeneity in stem cell populations or due to the effect of the changing niche environment remains largely unknown. By scRNA-Seq, we show that the age-related reduction in the MuSC pool is not stochastic, with different subpopulations being distinctly affected in aging. Using an in vivo allogeneic stem cell transplantation model, we show that exposure of MuSCs from old mice to a youthful niche environment significantly restores the gene expression of genes that are altered in aging. We show that age-related changes in the MuSC transcriptome are mainly driven by alterations in chromatin and transcription but are not due to posttranscriptional mechanisms affecting RNA stability. Furthermore, our data indicates that the portion of the genome that is activated in aging is significantly more responsive to restoration by niche factors compared to the repressed counterpart. Taken together, our data reveals that the niche environment plays a decisive role in controlling the transcriptional activity of MuSCs.

2023-01-25 | GSE171997 | GEO

ATAC-Seq of young and aged satellite cells

2022-03-15 | GSE171534 | GEO

Single-cell RNA-Sequencing of young and aged satellite cells, macrophages and fibro-adipogenic progenitor cells

2023-01-17 | GSE171794 | GEO

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

Changes of the muscle stem cell niche during aging

2021-11-10 | PXD023643 | 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

Restoration of CPEB4 Prevents Muscle Stem Cell Senescence during Aging

Project description: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.

2023-06-26 | PXD041614 | Pride

Depletion of SAM leading to loss of heterochromatin drives muscle stem cell ageing

Project description:The global loss of heterochromatin during aging has been observed in eukaryotes from yeast to humans, and this has been proposed to be one of the causes of aging. However, the cause of this age-associated loss of heterochromatin has remained enigmatic. Here we show that heterochromatin markers, including histone H3K9 di-/tri-methylation and HP1, decrease with age in murine muscle stem cells (MuSCs) as a consequence of the depletion of the methyl donor SAM. We find that restoration of intracellular SAM in aged MuSCs restores heterochromatin content to youthful levels and rejuvenates age-associated features including DNA damage accumulation, increased cell death, and defective muscle regeneration. SAM is not only a methyl group donor for transmethylation but it is also an aminopropyl donor for polyamine synthesis. Excessive consumption of SAM in polyamine synthesis may reduce its availability for transmethylation. Consistent with this premise, we observe that perturbation of increased polyamine synthesis by inhibiting spermidine synthase (Srm) restores the intracellular SAM content as well as heterochromatin formation, leading to improvements in aged MuSC function and regenerative capacity. Together, our studies demonstrate a direct causal link between polyamine metabolism and epigenetic dysregulation during MuSC aging.

2023-11-17 | GSE229853 | GEO

Depletion of SAM leading to loss of heterochromatin drives muscle stem cell ageing

2023-11-17 | GSE229851 | GEO