Mus musculus strain:C57/Bl6N
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ABSTRACT:
PROVIDER: PRJNA229481 | ENA |
REPOSITORIES: ENA
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Project description:Dynamic DNA methylation in cardiac myocyte development, maturation and disease
| PRJNA229470 | ENA
Project description:Dynamic DNA methylation in cardiac myocyte development, maturation and disease (ChIP-seq)
| PRJNA229480 | ENA
Project description:Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. Comparison of transcriptional programs of primary myocardial tissues sampled from neonatal mice and murine hearts undergoing post-injury regeneration, along with in vitro ESC-differentiated cardiomyocytes
2014-12-20 | E-GEOD-64403 | biostudies-arrayexpress
Project description:The HH16/17 chicken proepicardium (PE) gives rise to the embryonic epicardium (Epi) which significantly contributes formation of the coronary vasculature during cardiac development. In contrast to explanted Epi cells, explanted PE cells can undergo differentiation into a cardiac myocyte phenotype. In order to assess which genes are associated with PE differentiation into distinc cellular lineages, two interconnented microarray gene-expression series were performed. 1: Gene-expression profiles at 12, 24, 36, 48, 60, 72 and 120 hours during cardiac myocyte differentiation from including the HH16/17 PE (t0h) were determined by hybridizing Cy3 and Cy5 labelled amplified RNA to the ArkGen 20K oligo arrays in a 2-color looped experiment design, i.e., hybridization of successive time-points per array, including dye swaps, resulting in four technical replicates for each time point. 2: Gene expression changes during normal embryonic Epi maturation were assess by hybridizing Epi from stages HH25, HH29, HH32 and HH37 in all possible pair-wise combinations, including dye-swaps, leading to 6 replicates per time point. To allow for valid comparisons between the Epi and untreated PE differentiation, these two array series were connected via hybridization of both Epi stage HH25 and HH29 with the PE explant at 48 hours in culture, with dye swaps. Keywords: time course, cardiac myocyte differentiation, embryonic coronary vessel formation, cell type comparison, mRNA expression Proepicardium to cardiac myocyte differentiation: 16 arrays for 8 time points [t0h,t12h,t24h,t36h,t48h,t60h,t72h,t120h]; successive time points hybridized per array in a loop design with dye swaps + Embryonic epicardium dfferentiation: 12 arrays for 4 time points [HH25,HH29,HH32,HH37]; all possible sample combination were hybridized with dye swaps + Epicardium to Proepicardium data connection: 4 arrays; comparing HH25 and HH29 Epicardium to t48h Proepicardium with dye swaps.
2010-12-21 | E-GEOD-13923 | biostudies-arrayexpress
Project description:Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration.
2014-12-20 | GSE64403 | GEO
Project description:We used microarrays to detail genome-wide gene expression underlying cardiac myocyte pathologies and identified candidate genes and specific pathways affecting cardiac myopathies Keywords: transgenics, cardiac disease analysis
2009-07-25 | GSE12420 | GEO
Project description:Dynamic fibroblast state transitions underlie the heart’s fibrotic response, raising the possibility that tactical control of these transitions could alter maladaptive fibrotic outcomes. Transcriptome maturation by Muscleblind-like 1 (MBNL1) has emerged as a driver of differentiated cell states. Indeed, MBNL1 expression is elevated in conjunction with profibrotic transcripts in lineage traced myofibroblasts and modeling this gain in function by fibroblast-specific overexpression of an MBNL1 transgene induced a myofibroblast transcriptional identity in healthy hearts and promoted maladaptive myocyte remodeling and scar maturation following injury. Both fibroblast-specific and myofibroblast-specific loss of MBNL1 limited scar production and maturation, which was ascribed to negligible myofibroblast activity. MBNL1 deletion drove expansion of all quiescent cardiac fibroblast states and promoted mesenchymal stem cell characteristics while forced MBNL1 expression restricted state diversity by transitioning most fibroblasts to the most mature myofibroblast identity. These data suggest MBNL1 is a post-transcriptional switch controlling quiescent to myofibroblast transitions during cardiac wound healing.
2022-01-20 | GSE193308 | GEO
Project description:Methylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification associated recently with cardiac disease. In contrast, the role of 5-hydroxymethylcytosine (5-hmC) – 5-mC’s oxidation product – is unknown in the context of the heart. Here, we assess the hydroxymethylome in embryonic, neonatal, adult and hypertrophic mouse cardiomyocytes, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks during heart development and failure. DNA hydroxymethylation marks gene bodies of highly expressed genes and distal regulatory regions with enhanced activity. Pathological hypertrophy is characterized by a partial shift towards a fetal-like distribution pattern. We further demonstrate a regulatory function of TET2 and provide evidence that the expression of key cardiac genes, such as Myh7 is modulated by TET2-mediated 5-hmC deposition on the gene body and at enhancers in cardiac cells. We thus provide the first genome-wide analysis of 5-hmC in the cardiomyocyte, and establish the role of this epigenetic modification in heart development and disease
2016-06-21 | GSE79883 | GEO
Project description:Methylation at 5-cytosine (5-mC) is a fundamental epigenetic DNA modification associated recently with cardiac disease. In contrast, the role of 5-hydroxymethylcytosine (5-hmC) – 5-mC’s oxidation product – is unknown in the context of the heart. Here, we assess the hydroxymethylome in embryonic, neonatal, adult and hypertrophic mouse cardiomyocytes, showing that dynamic modulation of hydroxymethylated DNA is associated with specific transcriptional networks during heart development and failure. DNA hydroxymethylation marks gene bodies of highly expressed genes and distal regulatory regions with enhanced activity. Pathological hypertrophy is characterized by a partial shift towards a fetal-like distribution pattern. We further demonstrate a regulatory function of TET2 and provide evidence that the expression of key cardiac genes, such as Myh7 is modulated by TET2-mediated 5-hmC deposition on the gene body and at enhancers in cardiac cells. We thus provide the first genome-wide analysis of 5-hmC in the cardiomyocyte, and establish the role of this epigenetic modification in heart development and disease
2016-06-21 | GSE79882 | GEO