Muscle injury prepares stem cells for terminal myocyte differentiation through changes in gene expression and long-term changes in DNA methylation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE143891 | GEO | 2022/12/01
REPOSITORIES: GEO
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Project description:Muscle injury prepares stem cells for terminal myocyte differentiation through changes in gene expression and long-term changes in DNA methylation
| PRJNA601987 | ENA
Project description:Injury to muscle brings about the activation of stem cells, which then generate new myocytes to replace damaged tissue. We demonstrate that this activation is accompanied by a dramatic change in the stem-cell methylation pattern that prepares them epigenetically for terminal myocyte differentiation. These de- and de novo methylation events occur at regulatory elements associated with genes involved in myogenesis and are necessary for activation and regeneration. Local injury of one muscle elicits an almost identical epigenetic change in satellite cells from other muscles in the body, in a process mediated by circulating factors. Furthermore, this same methylation state is also generated in muscle stem cells (MuSCs) of female animals following pregnancy, even in the absence of any injury. Unlike the activation-induced expression changes, which are transient, the induced methylation profile is stably maintained in resident MuSCs and thus represents a molecular memory of previous physiological events that is probably programmed to provide a mechanism for long-term adaptation.
| S-EPMC9907067 | biostudies-literature
Project description:Past experience provides a rich source of predictive information about the world that could be used to guide and optimize ongoing perception. However, the neural mechanisms that integrate information coded in long-term memory (LTM) with ongoing perceptual processing remain unknown. Here, we explore how the contents of LTM optimize perception by modulating anticipatory brain states. By using a paradigm that integrates LTM and attentional orienting, we first demonstrate that the contents of LTM sharpen perceptual sensitivity for targets presented at memory-predicted spatial locations. Next, we examine oscillations in EEG to show that memory-guided attention is associated with spatially specific desynchronization of alpha-band activity over visual cortex. Additionally, we use functional MRI to confirm that target-predictive spatial information stored in LTM triggers spatiotopic modulation of preparatory activity in extrastriate visual cortex. Finally, functional MRI results also implicate an integrated cortical network, including the hippocampus and a dorsal frontoparietal circuit, as a likely candidate for organizing preparatory states in visual cortex according to the contents of LTM.
| S-EPMC3277524 | biostudies-literature
Project description:Reversible proline-directed phosphorylation at Ser/Thr-Pro motifs has an essential role in myogenesis, a multistep process strictly regulated by several signaling pathways that impinge on two families of myogenic effectors, the basic helix-loop-helix myogenic transcription factors and the MEF2 (myocyte enhancer factor 2) proteins. The question of how these signals are deciphered by the myogenic effectors remains largely unaddressed. In this study, we show that the peptidyl-prolyl isomerase Pin1, which catalyzes the isomerization of phosphorylated Ser/Thr-Pro peptide bonds to induce conformational changes of its target proteins, acts as an inhibitor of muscle differentiation because its knockdown in myoblasts promotes myotube formation. With the aim of clarifying the mechanism of Pin1 function in skeletal myogenesis, we investigated whether MEF2C, a critical regulator of the myogenic program that is the end point of several signaling pathways, might serve as a/the target for the inhibitory effects of Pin1 on muscle differentiation. We show that Pin1 interacts selectively with phosphorylated MEF2C in skeletal muscle cells, both in vitro and in vivo. The interaction with Pin1 requires two novel critical phospho-Ser/Thr-Pro motifs in MEF2C, Ser(98) and Ser(110), which are phosphorylated in vivo. Overexpression of Pin1 decreases MEF2C stability and activity and its ability to cooperate with MyoD to activate myogenic conversion. Collectively, these findings reveal a novel role for Pin1 as a regulator of muscle terminal differentiation and suggest that Pin1-mediated repression of MEF2C function could contribute to this function.
| S-EPMC2966067 | biostudies-literature
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:BackgroundSkeletal muscle atrophy is the major hallmark of cancer cachexia. The mechanisms underlying muscle wasting remain elusive in cachectic patients. Our research seeks to identify differentially expressed genes (DEGs) between non-cachectic and cachectic cancer patients and elucidate their functions.MethodsWe screened the DEGs of skeletal muscle between patients with and without cachexia from microarray data. Biological function of DEGs is analyzed through gene enrichment analysis, while an interaction network is constructed to visualize how genes are related. A Spearman's correlation analysis demonstrated the clinical significance of DUSP1 related to cancer cachexia. Skeletal muscle samples were collected and histomorphology studies were conducted. Function of DUSP1 on myogenesis was clarified by qPCR, western blotting, and immunofluorescence.ResultsWe screened 324 DEGs in skeletal muscle from patients with and without cachexia. The results of the gene enrichment analysis indicated that inflammatory cytokines and immune responses contribute significantly to the pathological condition of cachexia. DUSP1 was one of the key genes in the regulating network. DUSP1 protein and mRNA levels were increased significantly in skeletal muscle tissues from patients with cancer cachexia. DUSP1 expression in cachectic group was found to have negative correlation with SMA, prealbumin and BMI and positive correlation with TNFα, IL6 and weight loss. Significant changes of myogenesis related genes were observed in myocyte after DUSP1 was overexpressed and knocked down.ConclusionIn skeletal muscle of cachectic patients, DUSP1 expression was observed to be higher and thus DUSP1 promote muscle atrophy by inhibiting myogenesis. DUSP1 is expected to be a specific target in cancer cachexia for preventing and treating muscle atrophy.
| S-EPMC9663480 | biostudies-literature
Project description:Muscle injury causes long-term changes in stem cell DNA methylation [RRBS]
| PRJNA601988 | ENA
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. Here we show the changes in gene expression that accompany the changes in DNA methylation.
2022-12-01 | GSE142111 | GEO
Project description:These samples comprise the full analysis of liver function during response to thermal injury. Keywords: Time Course
2006-08-30 | GSE5647 | GEO
Project description:Myocyte enhancer factor 2 (MEF2) is a family of transcription factors that regulates many processes, including muscle differentiation. Due to its many target genes, MEF2D requires tight regulation of transcription activity over time and by location. Epigenetic modifiers have been suggested to regulate MEF2-dependent transcription via modifications to histones and MEF2. However, the modulation of MEF2 activity by lysine methylation, an important posttranslational modification that alters the activities of transcription factors, has not been studied. We report the reversible lysine methylation of MEF2D by G9a and LSD1 as a regulatory mechanism of MEF2D activity and skeletal muscle differentiation. G9a methylates lysine-267 of MEF2D and represses its transcriptional activity, but LSD1 counteracts it. This residue is highly conserved between MEF2 members in mammals. During myogenic differentiation of C2C12 mouse skeletal muscle cells, the methylation of MEF2D by G9a decreased, on which MEF2D-dependent myogenic genes were upregulated. We have also identified lysine-267 as a methylation/demethylation site and demonstrate that the lysine methylation state of MEF2D regulates its transcriptional activity and skeletal muscle cell differentiation.
| S-EPMC3874188 | biostudies-literature