Dissecting the Individual and Collective Regenerative Behavior of Muscle Stem Cells During Aging
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE121589 | GEO | 2019/08/30
REPOSITORIES: GEO
Similar Datasets
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 | PXD015616 | Pride
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
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
Project description:Dissecting the Individual and Collective Regenerative Behavior of Muscle Stem Cells During Aging
| PRJNA497842 | ENA
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
Project description:Social organisms form striking aggregation patterns, displaying cohesion, polarization, and collective intelligence. Determining how they do so in nature is challenging; a plethora of simulation studies displaying life-like swarm behavior lack rigorous comparison with actual data because collecting field data of sufficient quality has been a bottleneck. Here, we bridge this gap by gathering and analyzing a high-quality dataset of flocking surf scoters, forming well-spaced groups of hundreds of individuals on the water surface. By reconstructing each individual's position, velocity, and trajectory, we generate spatial and angular neighbor-distribution plots, revealing distinct concentric structure in positioning, a preference for neighbors directly in front, and strong alignment with neighbors on each side. We fit data to zonal interaction models and characterize which individual interaction forces suffice to explain observed spatial patterns. Results point to strong short-range repulsion, intermediate-range alignment, and longer-range attraction (with circular zones), as well as a weak but significant frontal-sector interaction with one neighbor. A best-fit model with such interactions accounts well for observed group structure, whereas absence or alteration in any one of these rules fails to do so. We find that important features of observed flocking surf scoters can be accounted for by zonal models with specific, well-defined rules of interaction.
| S-EPMC2906562 | biostudies-literature
Project description:Individual differences in learning can influence how animals respond to and communicate about their environment, which may nonlinearly shape how a social group accomplishes a collective task. There are few empirical examples of how differences in collective dynamics emerge from variation among individuals in cognition. Here, we use a naturally variable and heritable learning behavior called latent inhibition (LI) to show that interactions among individuals that differ in this cognitive ability drive collective foraging behavior in honey bee colonies. We artificially selected two distinct phenotypes: high-LI bees that ignore previously familiar stimuli in favor of novel ones and low-LI bees that learn familiar and novel stimuli equally well. We then provided colonies differentially composed of different ratios of these phenotypes with a choice between familiar and novel feeders. Colonies of predominantly high-LI individuals preferred to visit familiar food locations, while low-LI colonies visited novel and familiar food locations equally. Interestingly, in colonies of mixed learning phenotypes, the low-LI individuals showed a preference to visiting familiar feeders, which contrasts with their behavior when in a uniform low-LI group. We show that the shift in feeder preference of low-LI bees is driven by foragers of the high-LI phenotype dancing more intensely and attracting more followers. Our results reveal that cognitive abilities of individuals and their social interactions, which we argue relate to differences in attention, drive emergent collective outcomes.
| S-EPMC7395545 | biostudies-literature
Project description:We utilize RNA-Seq to evaluate how loss of Sestrin1,2, a conserved set of stress-inducible proteins, alters the metabolism and quiescent state of young (2-3 months) Muscle Stem Cells (MuSCs) during the regenerative response.
2020-11-26 | GSE162191 | GEO
Project description:Skeletal muscle stem cells (MuSCs) ensure the formation and homeostasis of skeletal muscle and are responsible for its growth and repair processes. For repair to occur, MuSCs must exit from quiescence, abandon their niche and asymmetrically and symmetrically divide to reconstitute the stem cell pool and give rise to muscle progenitors, respectively. The transcriptomes of pooled MuSCs have provided a rich source of information for describing the genetic programs underlying distinct static cell states; however, bulk microarray and RNA-seq afford only averaged gene expression profiles, which blur the heterogeneity and developmental dynamics of asynchronous MuSC populations. The granularity required to identify distinct cell types, states, and their dynamics can be provided by single-cell analysis. We were able to compare the transcriptomes of thousands of MuSCs and primary myoblasts isolated from homeostatic or regenerating muscles by single-cell RNA- sequencing. Using computational approaches, we could reconstruct dynamic trajectories and place, in a pseudotemporal manner, the transcriptomes of individual MuSC within these trajectories. This approach allowed for the identification of distinct clusters of MuSCs and primary myoblasts with partially overlapping but distinct transcriptional signatures, as well as the description of metabolic pathways associated with defined MuSC states.
2019-03-08 | GSE126834 | GEO
Project description:Skeletal muscle experiences a decline in lean mass and regenerative potential with age, in part due to intrinsic changes in progenitor cells. However, it remains unclear if age-related changes in progenitors persist across a differentiation trajectory or if new age-related changes manifest in differentiated cells. To investigate this possibility, we performed single cell RNA-seq on muscle mononuclear cells from young and aged mice and profiled muscle stem cells (MuSCs) and fibro/adipose progenitors (FAPs) after differentiation. Differentiation increased the magnitude of age-related change in MuSCs and FAPs, but also masked a subset of age-related changes present in progenitors. Using a dynamical systems approach and RNA velocity, we found that aged MuSCs follow the same differentiation trajectory as young cells, but stall in differentiation near a commitment decision. Our results suggest that age-related changes are plastic across differentiation trajectories and that fate commitment decisions are delayed in aged myogenic cells.
2021-04-16 | GSE145256 | GEO