Single cell RNA-seq comparing regeneration of young and aged skeletal muscles
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ABSTRACT:
PROVIDER: PRJNA942239 | ENA |
REPOSITORIES: ENA
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Project description:Abstract: Transcription factors (TFs) play key roles in regulating differentiation and function of stem cells, including muscle satellite cells (MuSCs), a resident stem cell population responsible for postnatal regeneration of the skeletal muscle. Sox11 belongs to the Sry-related HMG-box (SOX) family of TFs that play diverse roles in stem cell behavior and tissue specification. Analysis of single-cell RNA-sequencing (scRNA-seq) datasets identify a specific enrichment of Sox11 mRNA in differentiating but not quiescent MuSCs. Consistent with the scRNA-seq data, Sox11 levels increase during differentiation of murine primary myoblasts in vitro. scRNA-seq data comparing muscle regeneration in young and old mice further demonstrate that Sox11 expression is reduced in aged MuSCs. Age-related decline of Sox11 expression is associated with reduced chromatin contacts within the topologically associated domains. Unexpectedly, Myod1Cre-driven deletion of Sox11 in embryonic myoblasts has no effects on muscle development and growth, resulting in apparently healthy muscles that regenerate normally. Pax7CreER or Rosa26CreER driven (MuSC-specific or global) deletion of Sox11 in adult mice similarly has no effects on MuSC differentiation or muscle regeneration. These results identify Sox11 as a novel myogenic differentiation marker with reduced expression in quiescent and aged MuSCs, but the specific function of Sox11 in myogenesis remain to be elucidated.
2023-09-21 | GSE226907 | GEO
Project description:Skeletal muscle atrophy is one of the critical issues which elderly people face. The precise mechanism underlying muscle atrophy during aging is not fully understood. In order to identify miRNA whose expression is changed in age-associated muscle atrophy, we performed miRNA expression profiling of skeletal muscles in young and aged rats. Microarray analysis revealed differential miRNA expression in EDL and soleus muscles of aged rats compared with those of young rats. We next investigated whether the age-associated changes of miRNA expression observed in rats were recapitulated in mice and found that the expression level of miR-206 in EDL muscle and that of miR-196a in EDL and soleus muscles were respectively higher and lower in aged rodents than in young rodents. In mouse C2C12 myoblasts and myotubes, introduction of miR-196a decreased the protein level of Forkhead-box transcription factor Foxo1, a known target of miR-196a, indicating that miR-196a may regulate Foxo1 expression also in skeletal muscles. Furthermore, miR-196a overexpression exacerbated cell death caused by an exposure to hydrogen peroxide. Lastly, we demonstrated that expression of Foxo1 was elevated in EDL and soleus muscles of aged mice compared with those of young mice. These results suggest that miRNAs are involved in skeletal muscle atrophy during aging and that decreased miR-196a expression may protect skeletal muscle cells from oxidative stress in part through induction of Foxo1.
2016-08-31 | GSE70990 | GEO
Project description:Aging animals undergo a variety of changes in molecular processes. Among these, the cellular circadian clock has been shown to change as animals age. Moreover, there is evidence that also core circadian clock proteins could influence the ageing behavior of vertebrates. To investigate the interplay between aging and the circadian clock, we studied circadian mRNA expression in skeletal muscles from young (8 weeks) and aged (80 weeks) mice. In order to detect differences in circadian patterns, we used microarray-based transcriptome-wide time series of mRNA expression, containing 16 independent measurements for both young and aged animals. Each individual time point consists of total RNA from hind limb skeletal muscles from 3 different animals. Young and aged mice where entrained to 12 hr/12 hr light-dark conditions. From these mice, hind limb skeletal muscles were extracted at different times of day, in order to measure circadian mRNA expression patterns.
2016-03-31 | E-GEOD-75523 | biostudies-arrayexpress
Project description:Aging animals undergo a variety of changes in molecular processes. Among these, the cellular circadian clock has been shown to change as animals age. Moreover, there is evidence that also core circadian clock proteins could influence the ageing behavior of vertebrates. To investigate the interplay between aging and the circadian clock, we studied circadian mRNA expression in skeletal muscles from young (8 weeks) and aged (80 weeks) mice. In order to detect differences in circadian patterns, we used microarray-based transcriptome-wide time series of mRNA expression, containing 16 independent measurements for both young and aged animals. Each individual time point consists of total RNA from hind limb skeletal muscles from 3 different animals.
2016-03-31 | GSE75523 | GEO
Project description:Elevated glucocorticoids alter the skeletal muscle transcriptome to induce a myopathy characterized by muscle atrophy, muscle weakness, and decreased metabolic function. These effects are more likely to occur and be more severe in aged muscle. Resistance exercise can blunt development of glucocorticoid myopathy in young muscle, but the potential to blunt the signals initiating myopathy in aged muscle is unknown. To answer this, young (4-month-old) and aged (24-25-month-old) male C57BL/6 mice were randomized to receive either an intraperitoneal (IP) injection of dexamethasone (DEX; 2 mg/kg) or saline as a control. Two hours post-injections, tibialis anterior (TA) muscles of mice were subjected to unilateral high force contractions. Muscles were harvested four hours later. The glucocorticoid- and contraction-sensitive genes were determined by RNA sequencing. The number of glucocorticoid sensitive genes was similar between young and aged muscle. Contractions altered more glucocorticoid-sensitive genes in aged muscle, with this outcome primarily occurring when hormone levels were elevated. Glucocorticoid-sensitive gene programs altered by contractions were primarily related to metabolism in young mice and muscle size regulation and inflammation in aged mice. In silico analysis implied Peroxisome proliferator-activated receptor gamma-1 (PPARG) contributed to the contraction-induced changes in glucocorticoid-sensitive genes in aged muscle. Increasing PPARG expression in the TA of aged mice using Adeno-associated virus serotype 9 partially counteracted the glucocorticoid-induced reduction in Runt-related transcription factor 1 (Runx1) mRNA content, recapitulating the effects observed by contractions. Overall, these data contribute to our understanding of the mechanical regulation of the glucocorticoid transcriptome in aged skeletal muscle.
2024-10-28 | GSE269698 | GEO
Project description:Sarcopenia is the age-induced, progressive loss of skeletal muscle mass and function, which results in poor muscle performance. To better understand changes in skeletal muscles during sarcopenia, we performed a metabolomic analysis of skeletal muscle in young (8-week-old) and aged (28-month-old) mice using CE-TOFMS. Our data shows that the metabolites including glucose and polyamine metabolism were decreased in aged mice compared with young mice. In addition, neurotransmitter levels were higher in aged mice.
2019-05-06 | ST001179 | MetabolomicsWorkbench
Project description:To identify signaling pathways differencees between young and aged muscle stem cells
2022-01-13 | GSE145297 | GEO
Project description:Heterochronic blood exchange (HBE) has demonstrated that circulating factors restore youthful features to aged tissues. However, the systemic mediators of those rejuvenating effects remain poorly defined. We show that the beneficial effect of young blood on aged muscle regeneration was diminished when serum was depleted of extracellular vesicles (EVs). Whereas EVs from young animals rejuvenate aged cell bioenergetics and skeletal muscle regeneration, aging shifts EV subpopulation heterogeneity and compromises downstream benefits on recipient cells. Machine learning classifiers revealed that aging shifts the nucleic acid, but not protein, fingerprint of circulating EVs. Alterations in sub-population heterogeneity were accompanied by declines in transcript levels of the pro-longevity protein, α-Klotho, and injection of EVs improved muscle regeneration in a Klotho mRNA-dependent manner. These studies demonstrate that EVs play a key role in the rejuvenating effects of HBE and that Klotho transcripts within EVs phenocopy the effects of young serum on aged skeletal muscle.
2021-07-01 | GSE176478 | GEO
Project description:Age-related methylation changes have been identified in various tissues and organisms, yet the underlying DNA methylation alterations in muscle aging process have not been clearly clarified. Whilst, many studies revealed that the structural and functional changes in skeletal muscle during aging process started from the mid-point of lifespan. In this study, we used pigs aged 0.5 year and 7 years, representing young and middle-aged periods. Using methylated DNA immunoprecipitation sequencing, we performed comprehensive genome-wide DNA methylation profiling for longissimus dorsi muscle in young and middle-aged pigs. We found more genes showed differently methylated in genebody. In details, 185 human ortholog genes contained DMRs that located in the promoter region, while 657 genes and 1063 genes with DMRs in gene body showed hypermethylation and hypomethylation in MA pigs, respectively. From the gene enrichment analysis, genebody hypermethylated genes showed significant enrichment for several molecular functions such as M-bM-^@M-^XGTPase regulator activityM-bM-^@M-^Y, M-bM-^@M-^XATP bindingM-bM-^@M-^Y and M-bM-^@M-^Xprotein kinase activityM-bM-^@M-^Y. Notably, genebody hypomethylated genes showed significant enrichment for various proteolysis and protein catabolic process. However, genes with DMR in their promoter region were not significantly enriched in any biology process. Proteolysis-associated genes, such as FOXO3 and FGFR1, showed different genebody methylation and mRNA expression level in two age groups, which may contribute to muscle atrophy during aging. Especially, other tumorigenesis-associated genes including GPI and GRB2, exhibited increasing mRNA level in middle-aged pigs, suggesting the possible higher risk of having cancer in human middle-aged period. Our results will serve as a valuable resource in aging studies, promote pig as a model organism for human aging research and accelerate the considerable development of comparative animal models in aging research. We collected the longissimus dorsi muscles tissue from Jinhua pigs which aged 0.5 year and seven years and study the genome-wide DNA methylation difference and the genome-wide gene expression profile between the two age periods. This submission represents transcriptome component of study.
2014-08-02 | E-GEOD-49791 | biostudies-arrayexpress
Project description:RNA-seq of muscles from young and aged ATF4 mKO mice and littermate controls
| PRJNA876723 | ENA