Aging disrupts gene expression timing during muscle regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA747053 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15169919_1.fastq.gz | Fastqsanger.gz | |||
| SRR15169919_2.fastq.gz | Fastqsanger.gz | |||
| SRR15169920_1.fastq.gz | Fastqsanger.gz | |||
| SRR15169920_2.fastq.gz | Fastqsanger.gz | |||
| SRR15169921_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 57 |
Similar Datasets
Project description:Skeletal muscle function and regenerative capacity decline during aging, yet factors driving these changes are incompletely understood. Muscle regeneration requires temporally coordinated transcriptional programs to drive myogenic stem cells to activate, proliferate, fuse to form myofibers, and to mature myonuclei, restoring muscle function after injury. We assessed global changes in myogenic transcription programs distinguishing muscle regeneration in aged mice from young mice by comparing pseudotime trajectories from single-nucleus RNA sequencing of myogenic nuclei. Aging-specific differences in coordinating myogenic transcription programs necessary for restoring muscle function occur following muscle injury, likely contributing to compromised regeneration in aged mice. Differences in pseudotime alignment of myogenic nuclei when comparing aged to young mice via Dynamic Time-Warping revealed pseudotemporal differences becoming progressively more severe as regeneration proceeds. Disruptions in timing of myogenic gene expression programs may contribute to incomplete skeletal muscle regeneration and declines in muscle function as organisms age.
2023-06-12 | GSE180225 | GEO
Project description:Skeletal muscle function and regenerative capacity decline during aging, yet factors driving these changes are incompletely understood. Muscle regeneration requires temporally coordinated transcriptional programs to drive myogenic stem cells to activate, proliferate, fuse to form myofibers, and to mature as myonuclei, restoring muscle function after injury. We assessed global changes in myogenic transcription programs distinguishing muscle regeneration in aged mice from young mice by comparing pseudotime trajectories from single-nucleus RNA sequencing of myogenic nuclei. Aging-specific differences in coordinating myogenic transcription programs necessary for restoring muscle function occur following muscle injury, likely contributing to compromised regeneration in aged mice. Differences in pseudotime alignment of myogenic nuclei when comparing aged with young mice via dynamic time warping revealed pseudotemporal differences becoming progressively more severe as regeneration proceeds. Disruptions in timing of myogenic gene expression programs may contribute to incomplete skeletal muscle regeneration and declines in muscle function as organisms age.
| S-EPMC10277839 | biostudies-literature
Project description:Sugt1 loss skeletal muscle stem cells impairs muscle regeneration and causes premature muscle aging
| PRJNA972697 | ENA
Project description:Age-related alterations in the immune system are starting to emerge as key contributors to impairments found in aged organs. A decline in regenerative capacity is a hallmark of tissue aging, however the contribution of immune aging to regenerative failure is just starting to be explored. Here, we applied a strategy combining single-cell RNA-sequencing with flow cytometry and functional assays to perform a complete analysis of the immune environment in the aged regenerating skeletal muscle, with time and single cell resolution. Our results identified previously undescribed immune cell types in the skeletal muscle and revealed an unanticipated complexity and functional heterogeneity in immune populations, that have been regarded as homogeneous. Furthermore, we uncovered a profound remodeling of both myeloid and lymphoid compartments in aging. These discoveries challenge established notions on immune regulation of skeletal muscle regeneration, providing a new set of potential targets to improve skeletal muscle health and regenerative capacity in aging.
2024-10-18 | GSE279741 | GEO
Project description:MicroRNAs (miRNAs) are important in the regulation of many biological processes including muscle development. However, little is known regarding miRNA regulation of muscle regeneration. In mature murine tibialis anterior muscle following injury, 298 miRNAs were significantly changed during the time course of muscle regeneration including 86 that were altered greater than 10-fold as compared to uninjured muscle. Temporal miRNA expression patterns were identified and included inflammation-related miRNAs (miR-223 and -147) that increased immediately after injury; this pattern contrasted to that of mature muscle-specific miRNAs (miR-1, -133a and -499) that were abruptly decreased following injury and then up-regulated in later regenerative events. Another cluster of miRNAs were transiently increased in the early days of muscle regeneration. This included miR-351, a miRNA that was also transiently expressed during myogenic progenitor cell (MPC) differentiation in vitro. Based on computational predictions, further studies demonstrated that E2f3 was a target of miR-351 in myoblasts. Moreover, knockdown of miR-351 expression inhibited MPC proliferation and promoted apoptosis during MPC differentiation, whereas miR-351 overexpression protected MPC from apoptosis during differentiation. Collectively, these observations suggest that miR-351 is involved in both the maintenance of MPC proliferation and the transition of MPC into differentiated myotubes. Thus, a novel, time-dependent sequence of molecular events during skeletal muscle regeneration has been identified, i.e., miR-351 inhibits E2f3 expression, a key regulator of cell cycle progression and proliferation, and promotes MPC proliferation and protects early differentiating MPC from apoptosis, important events in the hostile tissue environment after acute muscle injury. Skeletal muscles are damaged and repaired repeatedly throughout life. Muscle regeneration maintains locomotor function during aging and delays the appearance of clinical symptoms in neuromuscular diseases, such as Duchenne muscular dystrophy. The capacity for skeletal muscle growth and regeneration is conferred by satellite cells located between the basal lamina and the sarcolemma of mature myofibers. Upon injury, satellite cells reenter the cell cycle, proliferate, and then exit the cell cycle either to renew the quiescent satellite cell pool or to differentiate into mature myofibers. Despite recent advances, genes involved in these processes are still largely unknown. Understanding the molecular mechanisms that regulate satellite cell activities could promote development of novel countermeasures to enhance muscle regeneration that is compromised by diseases or aging. Using a muscle injury mouse model, we profiled miRNA expression during muscle regeneration.
2012-04-24 | E-GEOD-37479 | biostudies-arrayexpress
Project description:The immune landscape of murine skeletal muscle regeneration and aging
| PRJNA1174189 | ENA
Project description:Circadian rhythms regulate cell differentiation and tissue regeneration; however, their implications in tissue regeneration remain elusive. Here, we present evidence that tissue regeneration efficiency is dependent on the circadian timing of injury affliction in a mouse model of muscle injury. We found that depletion of Per1 or Per2, members of the core circadian regulators in vertebrates, impaired mouse muscle regeneration and myoblast differentiation. Both Per1 and Per2 were necessary to maintain the expression level of Igf2, one of the critical regulators for myoblast differentiation, through epigenetic regulation at the Igf2 promoter and enhancer. Reflecting this, myoblast differentiation was promoted when differentiation was initiated while the level of Pers and Igf2 were high, compared with the time when their expression levels were low. Furthermore, muscle regeneration in the mouse was more efficient when chemical injury was inflicted at night when Pers were highly expressed, compared with morning injury. This study uncovers circadian timing-based control of myoblast differentiation and muscle regeneration.
2021-04-27 | GSE150785 | GEO
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:By satisfying bioenergetic demands, generating biomass, and providing metabolites serving as cofactors for chromatin modifiers, metabolism regulates adult stem cell biology. Here, we report that, branching off from glycolysis, the serine biosynthesis pathway (SBP) is activated in regenerating muscle stem cells (MuSCs). Gene inactivation and metabolomics revealed that Psat1, one of the three SBP enzymes, controls MuSCs activation and expansion of myogenic progenitors through production of the metabolite a-ketoglutarate (a-KG) and the a-KG-generated amino acid glutamine. Genetic ablation of Psat1 in MuSCs resulted in defective expansion of MuSCs and impaired regeneration. Psat1, a-KG, and glutamine were reduced in MuSCs of old mice and myoblasts of old individuals. a-KG or glutamine re-established appropriate muscle regeneration of adult Psat1-/- mice, old mice, and improved proliferation of old human myoblasts. These findings contribute insights into the metabolic role of Psat1 during muscle regeneration and suggest a-KG and glutamine as potential therapeutic interventions to ameliorate muscle regeneration during aging.
2024-12-18 | GSE248914 | GEO
Project description:By satisfying bioenergetic demands, generating biomass, and providing metabolites serving as cofactors for chromatin modifiers, metabolism regulates adult stem cell biology. Here, we report that, branching off from glycolysis, the serine biosynthesis pathway (SBP) is activated in regenerating muscle stem cells (MuSCs). Gene inactivation and metabolomics revealed that Psat1, one of the three SBP enzymes, controls MuSCs activation and expansion of myogenic progenitors through production of the metabolite a-ketoglutarate (a-KG) and the a-KG-generated amino acid glutamine. Genetic ablation of Psat1 in MuSCs resulted in defective expansion of MuSCs and impaired regeneration. Psat1, a-KG, and glutamine were reduced in MuSCs of old mice and myoblasts of old individuals. a-KG or glutamine re-established appropriate muscle regeneration of adult Psat1-/- mice, old mice, and improved proliferation of old human myoblasts. These findings contribute insights into the metabolic role of Psat1 during muscle regeneration and suggest a-KG and glutamine as potential therapeutic interventions to ameliorate muscle regeneration during aging
2024-12-18 | GSE248911 | GEO