Mus musculus
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ABSTRACT:
PROVIDER: PRJNA347652 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epigenetic stress responses induce muscle stem cell aging by Hoxa9 developmental signals
| PRJNA347647 | ENA
Project description:Epigenetic stress responses induce muscle stem cell aging by Hoxa9 developmental signals [RNA-seq]
| PRJNA344669 | ENA
Project description:Skeletal muscle atrophy is a debilitating condition that occurs with aging and disease but the underlying mechanisms are incompletely understood. Previous work determined that common transcriptional changes occur in muscle during atrophy induced by different stimuli. However, whether this holds true at the proteome level remains largely unexplored. Here, we find that, contrary to this earlier model, distinct atrophic stimuli (corticosteroids, cancer, and aging) induce largely different mRNA and protein changes during muscle atrophy in mice. Moreover, there is widespread transcriptome-proteome disconnect. Consequently, atrophy markers (atrogenes) identified in earlier microarray-based studies do not emerge from these proteomic surveys as the most relevantly associated with atrophy in all conditions. Rather, we identify proteins that are distinctly modulated by different types of atrophy (herein defined as “atroproteins”) such as the myokine CCN1/Cyr61, which regulates myofiber type switching during sarcopenia. Altogether, these integrated analyses indicate that different catabolic stimuli induce muscle atrophy via largely distinct mechanisms.
2022-02-22 | PXD027464 | Pride
Project description:ABSTRACT. Many cellular functions are ensured by the activity of multimolecular complexes and homeostatic mechanisms ensure their stoichiometric assembly. Disruption of individual complex components can perturb this process and induce local adaptive responses. In addition to cell-autonomous effects, such surveillance systems are also active at the organismal level: cellular stress in one tissue can be sensed systemically and lead to adaptive responses in other tissues during aging and disease, as found for muscle-to-central nervous system (CNS) stress signaling, Here, we have examined the local and systemic stress responses induced by the genetic perturbation of distinct molecular complexes, i.e. the sarcomere, mitochondrial complex I, proteasome, and VCP (valosin-containing protein) complex. Surprisingly, we find that a conserved stress response is induced locally in muscle and systemically following the muscle-specific RNAi for components of these diverse multimolecular complexes. These local and systemic responses are centered on the transcriptional induction of proteases and peptidases, many of which can degrade an aggregation-prone model protein, huntingtin-polyQ. The myokine Amyrel is a possible mediator of this muscle-to-CNS signaling because it was previously found to be triggered by proteasome stress in muscle and to regulate protease expression in the CNS. In agreement with this model, here we find that Amyrel expression is induced by perturbation of diverse multimolecular complexes. Moreover, Amyrel induction in muscle reduces pathogenic huntingtin-polyQ aggregates in the retina. These findings therefore suggest that Amyrel contributes to reshaping CNS proteostasis in response to perturbation of multimolecular complexes in skeletal muscle. Altogether, our study provides insight into a muscle-to-CNS systemic response that conveys the status of multimolecular complexes of skeletal muscle.
2025-10-22 | GSE299453 | GEO
Project description:Exercise Mitigates Skeletal Muscle Epigenetic Aging
| PRJNA732356 | ENA
Project description:The proteasome maintains protein quality during aging and disease. Challenges to proteasome function can be compensated by local proteasome stress responses. However, whereas proteasome stress is also sensed systemically is unknown. In Drosophila , we find that proteasome stress in skeletal muscle non-autonomously promotes the degradation of proteasome substrates in distant tissues during aging. Several muscle-secreted factors (myokines) are upregulated by proteasomal stress via C/EBP transcription factors, including the amylase Amyrel, which increases the circulating levels of the disaccharide maltose. Muscle-specific Amyrel overexpression promotes the degradation of proteasome substrates in the aging brain and retina via the transcriptional induction of chaperones and proteases. Conversely, RNAi for maltose transporters worsens proteostasis and reduces the expression of Amyrel-induced genes in the brain. Moreover, maltose preserves protein quality in cell culture and human cortical brain organoids challenged by thermal stress. Thus, proteasome stress in skeletal muscle mounts a systemic adaptive response via amylase/maltose signaling.
2021-02-12 | GSE149798 | GEO
Project description:The proteasome maintains protein quality during aging and disease. Challenges to proteasome function can be compensated by local proteasome stress responses. However, whereas proteasome stress is also sensed systemically is unknown. In Drosophila , we find that proteasome stress in skeletal muscle non-autonomously promotes the degradation of proteasome substrates in distant tissues during aging. Several muscle-secreted factors (myokines) are upregulated by proteasomal stress via C/EBP transcription factors, including the amylase Amyrel, which increases the circulating levels of the disaccharide maltose. Muscle-specific Amyrel overexpression promotes the degradation of proteasome substrates in the aging brain and retina via the transcriptional induction of chaperones and proteases. Conversely, RNAi for maltose transporters worsens proteostasis and reduces the expression of Amyrel-induced genes in the brain. Moreover, maltose preserves protein quality in cell culture and human cortical brain organoids challenged by thermal stress. Thus, proteasome stress in skeletal muscle mounts a systemic adaptive response via amylase/maltose signaling.
2021-02-12 | GSE149797 | GEO
Project description:As the actuator of movement and a key regulator of organismal metabolism, skeletal muscle is a site at which inflammatory responses must be carefully calibrated to counteract imposed stressors while preventing protracted functional impairments. Exercise, injury, and aging are common forms of stress associated with inflammation, particularly in skeletal muscle, yet the specific inducers and sensors driving such inflammation are not fully understood. Multi-pronged assessment of acute and chronic endurance-exercise models allowed us to evidence a role for MmSCs in transducing exercise-induced mechanical stress into local inflammatory responses. We identified the mechanosensitive ion channel Piezo1 as the molecular sensor of such mechanical stress. We also demonstrated that mechanosensing by stromal cells is necessary for appropriately timed inflammatory and myogenic responses to acute muscle injury and is associated with age-related muscle inflammation. Taken together, these findings highlight recognition of altered tissue stiffness by the Piezo1:MmSC pair as a fundamental mechanism of stress-induced immunomodulation in skeletal muscle.
2026-01-13 | GSE297515 | GEO
Project description:Hematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Epigenetic alterations are one of the hallmarks of HSC aging, and profiling of DNA methylation and histone modifications has provided potential mechanisms that contribute to HSC aging. Chromatin accessibility reflects a comprehensive transcriptional network operating in cells; however, it has not yet been investigated in HSC aging. Here we performed an integrated analysis of aged HSCs on transcriptome, chromatin accessibilities, and histone modifications. Alterations in chromatin accessibility preferentially took place in HSCs with aging, the cells at the top of hematopoietic hierarchy, suggesting that the age-associated alterations in chromatin accessibility are memorized in HSCs and are inherited to downstream progenitor cells. However, most genes with differentially accessible regions (DARs) were not actively transcribed and kept poised for activation in aged HSCs. Motifs of ATF/CREB, STAT, and CNC family transcription factors were significantly enriched at DARs in aged HSCs. These transcription factors are activated in response to external stresses such as cytokine and inflammation signals and oxidative stresses, suggesting that the long-term exposure to such stress signals have changed chromatin accessibility in HSCs to augment responses by such trained HSCs to subsequent stimuli. In contrast, aged HSC-specific gene expression occurred mainly at gene loci with poised accessible regions but not DARs without accompanying drastic chromatin reorganization, suggesting that altered cell-extrinsic stimuli or signals from aged niche largely account for this process. Our findings provide key epigenetic molecular insights into HSC aging and serve as a reference for future analysis.
2020-12-05 | GSE162659 | GEO
Project description:Loss of muscle mass and function—a hallmark of skeletal muscle aging—is known as sarcopenia. Moreover, mammalian aging is reportedly driven by loss of epigenetic information. However, the effect of epigenetic alterations on skeletal muscle homeostasis is unknown. In this study, we show that chronic elevation of global DNA methylation results in a myopathy-like phenotype and age-related changes in skeletal muscle. Overexpression of muscle de novo methyltransferase 3a (Dnmt3a) increased central nucleus-positive myofibers, predominantly in fast-twitch myofibers, and shifted muscle fiber type to stress-resistant slow-twitch myofibers, accompanied by upregulation of chemokine and immune system-related genes and reduced basal autophagy in skeletal muscle. Dnmt3a overexpression reduced muscle androgen receptor signaling, decreased muscle mass and strength, and impaired tolerance to endurance exercise with age. Network analysis identified Akt1 as a potential hub gene. Dnmt3a expression reduced sensitivity to starvation-induced muscle atrophy by suppressing the FoxO-regulated autophagy and ubiquitin–proteasome systems. These data suggest that increased global DNA methylation disrupts skeletal muscle homeostasis, promotes age-related decline in muscle function, and reduces muscle plasticity.
2025-01-16 | GSE244432 | GEO