Elevated H3K27ac in aged skeletal muscle tissue drives a fibrogenic conversion of muscle satellite cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA506722 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8239713_1.fastq.gz | Fastqsanger.gz | |||
| SRR8239713_2.fastq.gz | Fastqsanger.gz | |||
| SRR8239714_1.fastq.gz | Fastqsanger.gz | |||
| SRR8239714_2.fastq.gz | Fastqsanger.gz | |||
| SRR8239715_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
Similar Datasets
Project description:A variety of epigenetic alterations impairs functions of cells and tissues during aging, but it is not known if epigenetic alterations are associated with aging muscle. Here, we examined the changes of a panel of histone marks and found H3K27ac (an active enhancer mark) is markedly increased during aging in human skeletal muscle tissues. Our integrated analysis showed that enhancer activation during muscle aging is associated with the up-regulation of extracelluar matrix (ECM) genes, which may result in stiffness of the niche environment of satellite cells (SCs). An age-related fibrogenic conversion of geriatric SCs was observed through differential gene expression analysis. In mice, treatment of aging muscles with JQ1, an inhibitor of enhancer activation reverted the ECM up-regulation and fibrogenic conversion of SCs, suggesting that ECM increase in aging muscle is indeed a result of enhancer activation. The study here not only uncovered a novel aspect of muscle aging that is associated with enhancer remodeling but also highlighted JQ1 as a potential treatment approach for restoring SC function in aging muscle.
2019-08-15 | GSE122867 | GEO
Project description:Epigenetic alterations occur in various cells and tissues during aging, but it is not known if such alterations are also associated with aging in skeletal muscle. Here, we examined the changes of a panel of histone modifications and found H3K27ac (an active enhancer mark) is markedly increased in aged human skeletal muscle tissues. Further analyses uncovered that the H3K27ac increase and enhancer activation are associated with the up-regulation of extracellular matrix (ECM) genes; this may result in alteration of the niche environment for skeletal muscle stem cells, also called satellite cells (SCs), which causes decreased myogenic potential and fibrogenic conversion of SCs. In mice, treatment of aging muscles with JQ1, an inhibitor of enhancer activation, inhibited the ECM up-regulation and fibrogenic conversion of SCs and restored their myogenic differentiation potential. Altogether, our findings not only uncovered a novel aspect of skeletal muscle aging that is associated with enhancer remodeling but also implicated JQ1 as a potential treatment approach for restoring SC function in aging muscle.
| S-EPMC6718601 | biostudies-literature
Project description:Satellite cells are resident skeletal muscle stem cells responsible for muscle maintenance and repair. In resting muscle, satellite cells are maintained in a quiescent state. Satellite cell activation induces the myogenic commitment factor, MyoD, and cell cycle entry to facilitate transition to a population of proliferating myoblasts that eventually exit the cycle and regenerate muscle tissue. The molecular mechanism involved in the transition of a quiescent satellite cell to a transit-amplifying myoblast is poorly understood. We used microarrays to detail the global program of gene expression of in vivo satellite cell activation through muscle injury and identified RNA post-transcriptional regulation as a key component of satellite cell activation. Wild type or Sdc4-/- satellite cells were FACS isolated from resting muscle or from muscle 12h and 48h following barium chloride-induced muscle injury. 5000 cell equivalents of RNA was labeled and hybridized to MOE430v2 GeneChips (Affymetrix) and scanned as per manufacturers protocol. Probeset intensities were GCRMA normalized for further analysis including UPGMA hierarchical clustering, analysis of variance (ANOVA), and fold change.
2012-07-31 | E-GEOD-38870 | biostudies-arrayexpress
Project description:Elevated Extracellular Purine Nucleotides Impair Muscle Regeneration in Diabetic Mice by Suppressing Early Activation of Muscle Satellite Cells
| PRJNA733661 | ENA
Project description:Adult muscle stem cells (satellite cells) are required for adult skeletal muscle regeneration. A proper balance between quiescence, proliferation, and differentiation is essential for the maintenance of the satellite cell pool and their regenerative function. Although the ubiquitin-proteasome is required for most protein degradation in mammalian cells, how its dysfunction affects tissue stem cells remains unclear. Here, we investigated the function of the proteasome in satellite cells using mice lacking the crucial proteasomal component, Rpt3. Ablation of Rpt3 in satellite cells decreased proteasome activity. Proteasome dysfunction in Rpt3-deficient satellite cells impaired their ability to proliferate, survive and differentiate, resulting in defective muscle regeneration. We found that inactivation of proteasomal activity induced proliferation defects and apoptosis in satellite cells. Mechanistically, insufficient proteasomal activity upregulated the p53 pathway, which caused cell-cycle arrest. Our findings delineate a critical function of the proteasome system in maintaining satellite cells in adult muscle.
2018-10-10 | GSE114354 | GEO
Project description:The satellite cell is considered the major tissue-resident stem cell underlying muscle regeneration, however, multiple non-satellite cell myogenic progenitors have been identified. PW1/Peg3 is expressed in satellite cells as well as a subset of interstitial cells with myogenic potential termed PICs (PW1+ Interstitial Cells). PICs differ from satellite cells by their anatomical location (satellite cells are sublaminal and PICs are interstitial), they do not express any myogenic marker and arise from a Pax3-independent lineage. Upon isolation from juvenile muscle (1 to 3 weeks old), PICs are capable to form both skeletal and smooth muscle suggesting they constitute a more plastic population compared to satellite cells. We used microarrays to gain insight into the relantionship between PICs and satellite cells. PICs and satellite cells were isolated from 1-week old mouse muscle and subsequent RNA extraction was performed.
2012-09-01 | E-GEOD-40523 | biostudies-arrayexpress
Project description:(Abstract of publication submitted currently) To clarify molecular regulation of satellite cells, we performed genome-wide gene expression analysis of quiescent satellite cells isolated from mouse skeletal muscle by flow cytometry. We identified 53 novel quiescent satellite cell-specific genes whose expressions are sharply down-regulated upon activation. The gene list contains a number of cell surface molecules, transcriptional factors, and cytokines and other signal transduction molecules. We further confirmed that Odz4 and calcitonin receptor proteins were expressed by quiescent but not by activated satellite cells in vivo. Importantly, we found that Pax7+/calcitonin receptor+ satellite cells reappear in close association with regenerating myofibers 7 days after muscle damage, often outside the basal lamina. Moreover, an agonist of calcitonin receptor suppressed the activation of quiescent satellite cells on myofibers in in vitro culture, suggesting that calcitonin receptor signaling plays an important role in renewal and maintenance of satellite cells. Our results show the gene expression profile of quiescent satellite cells for the first time and reveal the temporal and spatial reappearance of a satellite cell pool. Experiment Overall Design: Satellite cells and non-satellite cells were examined. Totally three types of cells (groups), the satellite cells in quiescent and activated states and the non-satellite cells, were compared. Each has 4 replicates.
2008-06-12 | E-GEOD-3483 | biostudies-arrayexpress
Project description:Muscle satellite cells are a self-renewing pool of stem cells that give rise to daughter myogenic precursor cells in adult skeletal muscle. Published and preliminary data indicated that MyoD and p53 genes are involved in satellite cell differentiation. We would like to know what downstream genes of both transcription factors are affected in satellite cell-derived myoblasts (MyoD-/-, p53 -/-). Keywords: other
2005-09-07 | GSE3244 | GEO
Project description:Satellite cells are resident skeletal muscle stem cells responsible for muscle maintenance and repair. In resting muscle, satellite cells are maintained in a quiescent state. Satellite cell activation induces the myogenic commitment factor, MyoD, and cell cycle entry to facilitate transition to a population of proliferating myoblasts that eventually exit the cycle and regenerate muscle tissue. The molecular mechanism involved in the transition of a quiescent satellite cell to a transit-amplifying myoblast is poorly understood. We used microarrays to detail the global program of gene expression of in vivo satellite cell activation through muscle injury and identified RNA post-transcriptional regulation as a key component of satellite cell activation.
2012-08-01 | GSE38870 | GEO
Project description:Stimulation of the mouse hindlimb via the sciatic nerve was used to induce contractions for 4 hours to investigate acute muscle gene activation in a model of muscle phenotype conversion. Initial force production (1.6 + 0.1 g/g body weight) declined 45% within 10 min and was maintained for the remainder of the experiment. Force returned to initial levels upon completion of the study. An immediate-early growth response was present in the EDL (FOS, JUN, ATF3, MAFK) with a similar but attenuated pattern in the soleus. Transcript profiles showed decreased fast fiber specific mRNA (myosin heavy chains 2A, 2B; troponins T3, I; alpha-tropomyosin, m-creatine kinase) and increased slow transcripts (myosin heavy chain slow/1beta, troponin C, tropomyosin 3gamma) in the EDL. Histological analysis of the EDL revealed glycogen depletion without inflammatory cell infiltration or myofiber damage in stimulated vs. control muscles. Several fiber type specific transcription factors (EYA1, TEAD1, NFATc1 and c4, PPARG, PPARGC1alpha and beta, BHLHB2) increased in the EDL along with transcription factors characteristic of embryogenesis (KLF4, SOX17, TCF15, PKNOX1, ELAV). No established in vivo satellite cell markers or the genes activated during our parallel studies of satellite cell proliferation in vitro (CYCLINS A2, B2, C, E1, MyoD) increased in the stimulated muscles. These data indicated that onset of fast to slow phenotype conversion occurred in the EDL within 4 hours of stimulation without satellite cell recruitment or muscle injury but was driven by phenotype specific transcription factors from resident fiber myonuclei including activation of nascent developmental transcriptional programs.
2010-06-01 | GSE14381 | GEO