Muscle injury causes gene expression changes that are related to long-term changes in stem cell DNA methylation [RNA-Seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE142111 | GEO | 2022/12/01
REPOSITORIES: GEO
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Project description:Injury to muscle brings about the activation of stem cells, which then generate new myocytes to replace the damaged tissue. We now demonstrate that this activation causes a dramatic change in the stem cell methylation pattern that prepares them epigenetically for terminal myocyte differentiation. These demethylation and de novo methylation events occur at regulatory elements associated with genes involved in myogenesis. Local injury of one muscle brings about an almost identical epigenetic change in satellite cells from other muscles in the body, as well. Furthermore, this same methylation state is also generated in muscle stem cells of female animals following full-term pregnancy, even in the absence of any injury. In all of these cases, which appear to be mediated by circulating factors, the new methylation profile is then stably maintained in resident muscle stem cells and thus represents a molecular memory of previous physiological events that is probably programmed to provide a mechanism for adapting to the environment.
2022-12-01 | GSE143890 | GEO
Project description:MicroRNA expression profiling during muscle stem cell activation. Quiescent muscle stem cells from uninjured muscles and activated muscle stem cells from injured muscles at indicated time points were isolated by FACS. MicroRNA expression profiling during muscle stem cell activation using real-time PCR based miRNA arrays. Muscle stem cells were harvested at indicated time points (0hr, 36hr, 60hr and 72hr) after injury. 3 technical replicates were performed. Supplementary files: Raw data (Ct) and complete processed data (dCt, ddCt, fold-change) by platform.
2012-01-01 | E-GEOD-26780 | biostudies-arrayexpress
Project description:Muscle stem cells, also known as satellite cells, are largely non-proliferative in uninjured skeletal muscle but transition at sites of injury into rapidly dividing progenitors that mediate muscle repair. As early events in satellite cell activation are rate-limiting for recovery from muscle damage, there is substantial interest in discovering their molecular driver(s). Using a comparative transcriptomic approach, we identified a prominent Fos signature in recently activated muscle satellite cells, which was rapidly and transiently induced by muscle damage. Functional interrogation using complementary genetic mouse models revealed that FOS is required for efficiently initiating key stem cell functions, including cell cycle entry, stem/progenitor cell expansion, and regeneration of muscle after injury. Transcriptional profiling further revealed that FOS activates critical gene circuits that stimulate cell migration, proliferation, and differentiation while simultaneously repressing quiescence-promoting gene signatures. Pharmacological and genetic disruption of one of these FOS-activated target genes, mono-ADP Ribosyl-Transferase 1 (Art1), in freshly isolated satellite cells substantially diminished cell cycle entry and expansion of the pool of regenerative stem cells. Together, these data implicate FOS as a crucial inducer of early-acting, pro-regenerative gene targets and highlight new transcriptional and post-translational modification events necessary for optimal injury-activated muscle stem cell regenerative responses.
2021-01-27 | GSE119895 | GEO
Project description:Muscle stem cells, also known as satellite cells, are largely non-proliferative in uninjured skeletal muscle but transition at sites of injury into rapidly dividing progenitors that mediate muscle repair. As early events in satellite cell activation are rate-limiting for recovery from muscle damage, there is substantial interest in discovering their molecular driver(s). Using a comparative transcriptomic approach, we identified a prominent Fos signature in recently activated muscle satellite cells, which was rapidly and transiently induced by muscle damage. Functional interrogation using complementary genetic mouse models revealed that FOS is required for efficiently initiating key stem cell functions, including cell cycle entry, stem/progenitor cell expansion, and regeneration of muscle after injury. Transcriptional profiling further revealed that FOS activates critical gene circuits that stimulate cell migration, proliferation, and differentiation while simultaneously repressing quiescence-promoting gene signatures. Pharmacological and genetic disruption of one of these FOS-activated target genes, mono-ADP Ribosyl-Transferase 1 (Art1), in freshly isolated satellite cells substantially diminished cell cycle entry and expansion of the pool of regenerative stem cells. Together, these data implicate FOS as a crucial inducer of early-acting, pro-regenerative gene targets and highlight new transcriptional and post-translational modification events necessary for optimal injury-activated muscle stem cell regenerative responses.
2021-01-27 | GSE119695 | GEO
Project description:Skeletal muscle is a plastic tissue, adapting to different stimuli. Mechanical overload causes muscle hypertrophy and substantial changes in gene expression. We perform a time course analysis following synergistic ablation surgery to induce compensatory hypertrophy in the plantaris muscle in satellite cell depleted mice and wild-type mice. Microarray was used to determine the different expressed genes in skeletal muscle with or without satellite cell following mechanical overload.
2021-07-12 | GSE153542 | GEO
Project description:Cardiotoxin (CTX)-induced acute muscle injury is a paradigmatic self-limiting sterile injury model for exploring the tissue regeneration process, which consists of a series of tightly-regulated events, including an initial inflammatory response the activation of muscle stem cells (MuSCs, also termed satellite cells) during the early stage after injury, as well as later inflammation resolution along with MuSC proliferation and differentiation. This study set out to determine the potential impact of lipid 11,12-EET on murine MuSCs function.
2024-07-29 | GSE246007 | GEO
Project description:Purpose: The goal of this study was to determine the gene expression changes that occur over 7 days in parralyzed muscle in response to isometric contraction elicited by electrical stimulation initiated 4 months after spinal cord injury and to compare such changes to those observed in a normal muscle subjected to overload. Methods: Electrical stimulation of the soleus and plantaris muscle was stimulated in female rats with complete transection of the spinal cord at the interspace between the 9th and 10th thoracic vertebrae. Stimulation was begun 16 weeks after spinal cord transection and produced near-isometric contraction of soleus, plantaris and tibialis anterior. Muscle was analyzed at 1, 2 and 7 days after starting exercise with electrical stimulation. To provide a baseline reference for gene expression at 16 weeks after spinal cord injury, muscle was also analysed from an additional group of spinal cord transected animals. One additional group of animals with a sham-spinal cord injury was included to provide information about gene expression in neurologically intact animals of similar age. In parallel studies, rats underwent bilateral gastrocnemius ablation to overload soleus and plantaris, or a sham ablation as a control. Muscle was analyzed at 1, 3 and 7 days after gastrocnemius ablation or sham-ablation. Gene expression was determined using Affymetrix Rat Exon microarrays. For each group of animals, microarray analysis was performed for soleus muscle for each of 3 separate animals, using one array per animal. Control sammples for the spinal cord injured groups included a group of animals with a Sham-spinal cord injury, and a group of spinal cord injured animals that did not get electrical stimulation. The comparator for determining fold-change expression values was the spinal cord injured group that did not receive electrical stimulation. For each day after gastrocnemius ablation, a control was included that received all procedures needed for this ablation except cutting the distal insertion of the gastrocnemius into the Achilles tendon to control for effects of the surgery on gene expression.
2013-03-30 | E-GEOD-37476 | biostudies-arrayexpress
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: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:he ability to induce pluripotent stem cells from committed, somatic human cells provides tremendous potential for regenerative medicine. However, there is a defined neoplastic potential inherent to such reprogramming that must be understood and may provide a model for understanding key events in tumorigenesis. Using genome-wide assays, we identify cancer-related epigenetic abnormalities that arise early during reprogramming and persist in induced pluripotent stem cell (iPS) clones. These include hundreds of abnormal gene silencing events, patterns of aberrant responses to epigenetic-modifying drugs resembling those for cancer cells, and presence in iPS and partially reprogrammed cells of cancer-specific gene promoter DNA methylation alterations. Our findings suggest that by studying the process of induced reprogramming, we may gain significant insight into the origins of epigenetic gene silencing associated with human tumorigenesis, and add to means of assessing iPS for safety. Methylation was analyzed using Illumina's 27k Infinium platform for direct detection of methylation after bisulfite conversion. The overall methylation status was determined for several iPS lines and the pool cells from which they are derived. These methylation levels can be compared directly to those of cultured stem cells, differentiated cells and cancer cell lines.
2011-06-16 | E-GEOD-29872 | biostudies-arrayexpress