Comparative analysis of genome-wide gene expression profiles in hearts of C57B/6J mice
Ontology highlight
ABSTRACT: The neonatal murine heart is able to regenerate after severe injury, however this capacity quickly diminishes within the first week of life. Since DNA methylation is one of epigenetic mechanisms that plays a crucial role in cell development and gene expression regulation, we explored the changes of DNA methylation and gene expression patterns which accompany the loss of the transient regenerative potential in the heart. We used MeDIP-chip approach in order to compare global DNA methylation profiles in the murine hearts at 1 day and 7 days after birth, as well as, in hearts of mice at the age of 2 and 8 weeks. The comparison exposed a number of DNA promoter regions significantly changing their DNA methylation status between these time-points. As the result a number of DMRs have been identified which show an overrepresentation of genes which are critical for proper heart maturation and muscle development. The methylome transition from d1 to d7 is characterized by the excess of gene regulatory regions which gain over those that lose DNA methylation, thus suggesting that a number of genes active at d1 are repressed at d7.
Project description:The neonatal murine heart is able to regenerate after severe injury, however this capacity quickly diminishes within the first week of life. Since DNA methylation is one of epigenetic mechanisms that plays a crucial role in cell development and gene expression regulation, we explored the changes of DNA methylation and gene expression patterns which accompany the loss of the transient regenerative potential in the heart. We used MeDIP-chip approach in order to compare global DNA methylation profiles in the murine hearts at 1 day and 7 days after birth, as well as, in hearts of mice at the age of 2 and 8 weeks. The comparison exposed a number of DNA promoter regions significantly changing their DNA methylation status between these time-points. As the result a number of DMRs have been identified which show an overrepresentation of genes which are critical for proper heart maturation and muscle development. The methylome transition from d1 to d7 is characterized by the excess of gene regulatory regions which gain over those that lose DNA methylation, thus suggesting that a number of genes active at d1 are repressed at d7.
Project description:Background: To better understand the role DNA methylation plays in regulating gene expression in the developng heart and furthermore the role it plays in heart development we performed genome wide DNA methylation profiling of embryonic hearts at embryonic day (E)11.5 and E14.5 using methyl sensitive tiny fragment enrichment coupled with massive parallel sequencing by using the methyl-sensitive restriction enzyme HpyCH4IV, recognition site 'ACGT'. Results: We found that global methylation remains stable at analyzed 'ACGT' sites (1.64 million site) in developing hearts between E11.5 and E14.5. However, differential methylation was identified at individual loci enriched at genes involved in heart development suggesting a role for DNA methylation in the developing heart. Used Methyl Sensitive Tiny Fragment Enrichment/Massive Parallel Sequencing (MSFE/MPS) to assay methylation at 'ACGT' sites throughout the genome and generate a developmental profile of DNA methylation in the embryonic heart and to identify differences between developing mouse hearts at E11.5 and E14.5.
Project description:Background: To better understand the role DNA methylation plays in regulating gene expression in the developng heart and furthermore the role it plays in heart development we performed genome wide DNA methylation profiling of embryonic hearts at embryonic day (E)11.5 and E14.5 using methyl sensitive tiny fragment enrichment coupled with massive parallel sequencing by using the methyl-sensitive restriction enzyme HpyCH4IV, recognition site 'ACGT'. Results: We found that global methylation remains stable at analyzed 'ACGT' sites (1.64 million site) in developing hearts between E11.5 and E14.5. However, differential methylation was identified at individual loci enriched at genes involved in heart development suggesting a role for DNA methylation in the developing heart.
Project description:Antenatal hypoxia has critial impacts on fetal heart development. The molecular mechanism of the antenaltal hypoxia effect on the heart development is still unknown. We performed DNA methylome and transcriptome analyses of antenatal hypoxia induced rat fetal and adult offspring hearts to understand the hypoxia-mediated epigenomic programming in the heart development. Heart tissue from fetal (E21) and adult rat (5 months old) were collected. mRNA and genomic DNA methylation profiles of the heart tissue were generated by RNAseq and reduced representation bisulfite seuqencing (RRBS) techniques. We found 323 and 112 differential expressed genes between control and hypoxia groups in the fetal and adult hearts, respectively. Meanwhile, 2828 and 2193 differential methylated regions were identified in the fetal and adult hearts. Furthermore, opposite gobal DNA methylation pattern changes in transcription start site regions (TSS ± 1kb) were observed between fetal and adult hearts. Combining transcriptome, data indicates a significant difference in the responding genes and pathways between fetal and adult hearts in responding to the antenatal hypoxia. Our study provides an initial framework and new insights into fetal hypoxia-mediated epigenetic programming of pro-inflammatory phenotype in the heart development, linking antenatal stress, and developmental programming of heart vulnerability to disease later in life.
Project description:Antenatal hypoxia has critial impacts on fetal heart development. The molecular mechanism of the antenaltal hypoxia effect on the heart development is still unknown. We performed DNA methylome and transcriptome analyses of antenatal hypoxia induced rat fetal and adult offspring hearts to understand the hypoxia-mediated epigenomic programming in the heart development. Heart tissue from fetal (E21) and adult rat (5 months old) were collected. mRNA and genomic DNA methylation profiles of the heart tissue were generated by RNAseq and reduced representation bisulfite seuqencing (RRBS) techniques. We found 323 and 112 differential expressed genes between control and hypoxia groups in the fetal and adult hearts, respectively. Meanwhile, 2828 and 2193 differential methylated regions were identified in the fetal and adult hearts. Furthermore, opposite gobal DNA methylation pattern changes in transcription start site regions (TSS ± 1kb) were observed between fetal and adult hearts. Combining transcriptome, data indicates a significant difference in the responding genes and pathways between fetal and adult hearts in responding to the antenatal hypoxia. Our study provides an initial framework and new insights into fetal hypoxia-mediated epigenetic programming of pro-inflammatory phenotype in the heart development, linking antenatal stress, and developmental programming of heart vulnerability to disease later in life.
Project description:Data set contains samples from isolated cells of murine hearts after myocardial infarction (LAD surgery). We used Col1a2 tracing system to mark Collagen expressing cells within d3 to d7 post infarct. In brief, adult Col1a2-ERT2+/-;mT/mG mice, at an age of 12 weeks (n=4) as well as aged animals with 88-91 weeks (n=4) were used. Left anterior descending coronary artery ligation surgery was performed, inducing myocardial infarction. Homeostasis animals were not operated. For Cre induction we injected 2mg Tamoxifen from d3 to d7 post surgery. All animals were sacrificed 28d post injury. Murine scRNA-seq libraries were prepared using Chromium Single Cell 3′ v3 Reagent Kit (10X Genomics), according to manufacturer’s protocols. Raw reads were mapped against a customized version of mm10 (GRCm38.p4) containing sequences of EGFP and tdTomato.
Project description:This study examines the global transcriptomic profiles in peripheral blood of Papua New Guinea newborns at birth (D0) comparing with follow up at day 1 (D1), day 3 (D3), or day 7 (D7) post birth.
2019-03-20 | GSE123070 | GEO
Project description:DNA Methylation of Murine Hearts in the Hybrid Mouse Diversity Panel
Project description:Fibroblasts produce the majority of collagen in the heart and are thought to regulate extracellular matrix (ECM) turnover. However, the in vivo role of fibroblasts in structuring the basal ECM network is poorly understood. To examine the effects of fibroblast loss on the microenvironment in the adult murine heart, we generated mice with reduced fibroblast numbers and evaluated the tissue microenvironment during homeostasis and after injury. We determined that a 60-80% reduction in fibroblasts numbers did not overtly change the fibrillar collagen network but did alter the distribution and abundance of type VI collagen, a microfibrillar collagen that forms an open network with the basement membrane. In fibroblast ablated mice, myocardial infarction did not result in ventricular wall rupture, and heart function was more effectively preserved during angiotensin II/phenylephrine (AngII/PE) induced fibrosis. Analysis of cardiomyocyte contractility demonstrated weaker contractions and slower calcium release and reuptake in uninjured and AngII/PE infused fibroblast ablated animals. Moreover, fibroblast ablated hearts have a similar gene expression prolife to hearts with exercise-induced and physiological hypertrophy after AngII/PE infusion. These results suggest that hearts are resilient to a significant degree of fibroblast loss and that fibroblasts can directly impact cardiomyocyte function. Furthermore, a reduction in fibroblasts may have cardioprotective effects heart after injury suggesting that manipulation of the number of fibroblasts may have therapeutic value.