Effect of depletion of Hmgcs2 on gene expression in neonatal mouse heart
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE206797 | GEO | 2022/09/20
REPOSITORIES: GEO
Similar Datasets
Project description:Cy3-labeled cDNA obtained from four pools of three hearts of neonatal C57BL Cx43 null mice were compared to Cy3-labeled cDNA obtained from four pools of three hearts of neonatal C57BL wildtype mice through Cy5-labeled sample reference prepared at once for the entire experiment from aorta, brain, heart, kidney, liver, lung, ovary/testicles, spleen, and stomach - equal amounts from adult male and female C57BL mice. Keywords = Cx32 null vs wildtype neonatal mouse heart
2010-06-05 | E-GEOD-1961 | biostudies-arrayexpress
Project description:Cy3-labeled cDNA obtained from four pools of three hearts of neonatal C57BL Cx43 null mice were compared to Cy3-labeled cDNA obtained from four pools of three hearts of neonatal C57BL wildtype mice through Cy5-labeled sample reference prepared at once for the entire experiment from aorta, brain, heart, kidney, liver, lung, ovary/testicles, spleen, and stomach - equal amounts from adult male and female C57BL mice. Keywords = Cx32 null vs wildtype neonatal mouse heart Keywords: parallel sample
2004-11-13 | GSE1961 | GEO
Project description:Background: The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. To uncover the molecular mechanisms underlying neonatal heart regeneration, we compared the transcriptomes and epigenomes of regenerative and non-regenerative mouse hearts over a 7-day time period following myocardial infarction. Methods: RNA-Seq, H3K27ac ChIP-Seq and H3K27me3 ChIP-Seq were performed on ventricular samples from regenerative P1 or non-regenerative P8 mouse hearts at +1.5d, +3d and +7d after MI or Sham surgery to assemble the transcriptome, active chromatin and repressed chromatin landscapes during neonatal heart regeneration. Dynamic enhancer landscapes from mouse hearts during cardiac development were analyzed using data from ENCODE. Effects on cardiomyocyte proliferation and cardiac function from selected factors identified in this study were tested using BrdU/EdU pulse-labeling or mouse models coupled with immunohistochemistry and echocardiography. Results: By integrating gene expression profiles with histone marks associated with active or repressed chromatin, we identified transcriptional programs underlying neonatal heart regeneration and the blockade to regeneration in later life. Our results reveal a unique immune response in regenerative hearts and an embryonic cardiogenic gene program that remains active during neonatal heart regeneration. Among the unique immune factors and embryonic genes associated with cardiac regeneration, we identified Ccl24, which encodes a cytokine, and Igf2bp3, which encodes an RNA-binding protein, as previously unrecognized regulators of cardiomyocyte proliferation. Conclusions: Our data provide insights into the molecular basis of neonatal heart regeneration and identify genes that might be modulated to promote heart regeneration.
2019-07-15 | GSE123867 | GEO
Project description:Background: The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. To uncover the molecular mechanisms underlying neonatal heart regeneration, we compared the transcriptomes and epigenomes of regenerative and non-regenerative mouse hearts over a 7-day time period following myocardial infarction. Methods: RNA-Seq, H3K27ac ChIP-Seq and H3K27me3 ChIP-Seq were performed on ventricular samples from regenerative P1 or non-regenerative P8 mouse hearts at +1.5d, +3d and +7d after MI or Sham surgery to assemble the transcriptome, active chromatin and repressed chromatin landscapes during neonatal heart regeneration. Dynamic enhancer landscapes from mouse hearts during cardiac development were analyzed using data from ENCODE. Effects on cardiomyocyte proliferation and cardiac function from selected factors identified in this study were tested using BrdU/EdU pulse-labeling or mouse models coupled with immunohistochemistry and echocardiography. Results: By integrating gene expression profiles with histone marks associated with active or repressed chromatin, we identified transcriptional programs underlying neonatal heart regeneration and the blockade to regeneration in later life. Our results reveal a unique immune response in regenerative hearts and an embryonic cardiogenic gene program that remains active during neonatal heart regeneration. Among the unique immune factors and embryonic genes associated with cardiac regeneration, we identified Ccl24, which encodes a cytokine, and Igf2bp3, which encodes an RNA-binding protein, as previously unrecognized regulators of cardiomyocyte proliferation. Conclusions: Our data provide insights into the molecular basis of neonatal heart regeneration and identify genes that might be modulated to promote heart regeneration.
2019-07-15 | GSE123863 | GEO
Project description:The adult heart responds to injury by scarring with consequent loss of contractile function, whereas the neonatal heart possesses the ability to regenerate. We compared the immune response to injury in neonatal and adult mouse hearts and discovered that the PD1/PD-L1 immune checkpoint pathway is highly activated in regenerative hearts but is silenced in later life. Deletion of the PD1 receptor or inactivation of its PD-L1 ligand prevented regeneration of neonatal hearts after injury. Our findings reveal a previously unrecognized role of the PD1/PD-L1 pathway in the control of heart regeneration through modulating T cell activity and inflammation following injury and provide new inroads into the control of adult tissue regeneration.
2023-06-01 | GSE207215 | GEO
Project description:The adult heart responds to injury by scarring with consequent loss of contractile function, whereas the neonatal heart possesses the ability to regenerate. We compared the immune response to injury in neonatal and adult mouse hearts and discovered that the PD1/PD-L1 immune checkpoint pathway is highly activated in regenerative hearts but is silenced in later life. Deletion of the PD1 receptor or inactivation of its PD-L1 ligand prevented regeneration of neonatal hearts after injury. Our findings reveal a previously unrecognized role of the PD1/PD-L1 pathway in the control of heart regeneration through modulating T cell activity and inflammation following injury and provide new inroads into the control of adult tissue regeneration.
2023-06-01 | GSE207289 | GEO
Project description:The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury but lose it after a week of life, which has been utilized as a valuable model to explore the cues for heart regeneration. More and more researches indicated that glycoprotein played an important role in cardiac regeneration. Elucidating the glycosylation processes associated with heart regeneration will be beneficial for the molecular mechanism studies of heart regeneration as well as discovery of potential therapeutic strategies for human cardiac diseases. In this work, an integrated glycoproteomic and proteomic analysis were performed to investigate the differences in glycoprotein abundances and site-specific glycosylation occupancy between neonatal day 1 (P1) and day 7 (P7) of mouse hearts. The intact glycoepeptides were enriched and identified in both P1 and P7 hearts. To screen for differentially regulated glycoproteins, we compared the expression levels of intact glycopeptides between P1 and P7 hearts using label free quantification. Eventually, the glycosylation occupancy of site-specific N-glycans were obtained by comparing the alterations of intact glycopeptides with their corresponding protein expression levels obtained from global proteomic analysis. These altered glycosylation patterns among proteins between P1 and P7 mouse hearts have a significant potential to aid our understanding of the regenerative capacity loss in neonatal mouse hearts during the first week, thus leading to novel therapeutic approaches to recover the capacity.
2020-05-26 | PXD017139 | Pride
Project description:The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. Neonatal heart regeneration is orchestrated by multiple cell types intrinsic to the heart, as well as immune cells that infiltrate the heart after injury. To elucidate the transcriptional responses of the different cellular components of the mouse heart following injury, we performed single cell RNA-sequencing on neonatal hearts at various time points following myocardial infarction, and coupled the results with bulk tissue RNA-sequencing data collected at the same time points. Concomitant single cell ATAC-sequencing exposed underlying dynamics of open chromatin landscapes and regenerative gene regulatory networks of diverse cardiac cell types, and revealed previously unknown mediators of cardiomyocyte proliferation, angiogenesis and fibroblast activation. Together, our data provide a transcriptional basis for neonatal heart regeneration at single cell resolution and suggest new strategies for enhancing cardiac function in response to injury.
2020-12-08 | GSE153480 | GEO
Project description:The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. Neonatal heart regeneration is orchestrated by multiple cell types intrinsic to the heart, as well as immune cells that infiltrate the heart after injury. To elucidate the transcriptional responses of the different cellular components of the mouse heart following injury, we performed single cell RNA-sequencing on neonatal hearts at various time points following myocardial infarction, and coupled the results with bulk tissue RNA-sequencing data collected at the same time points. Concomitant single cell ATAC-sequencing exposed underlying dynamics of open chromatin landscapes and regenerative gene regulatory networks of diverse cardiac cell types, and revealed previously unknown mediators of cardiomyocyte proliferation, angiogenesis and fibroblast activation. Together, our data provide a transcriptional basis for neonatal heart regeneration at single cell resolution and suggest new strategies for enhancing cardiac function in response to injury.
2020-12-08 | GSE153479 | GEO
Project description:Adult mammalian hearts do not regenerate following ischemic injury, causing permanent damage to the myocardium, often leading to heart failure. In contrast, neonatal mouse hearts can fully regenerate after injury, however this ability is lost shortly after birth. Loss of regenerative capacity coincides with profound changes in the epigenetic landscape. Yet, the mechanisms controlling cardiomyocyte proliferation remain poorly understood. To identify epigenetic mechanisms that underlie cardiomyocyte regeneration in response to ischemic injury, we subjected mice to sham or ischemia-reperfusion injury (IR) and performed RNA-Seq at multiple timepoints after injury. Multiple SWI/SNF chromatin remodeling complex subunits were upregulated after IR, including the AT-rich interactive domain-containing protein 1A (Arid1a), which has previously been implicated in tissue regeneration. Here, we show that Arid1a is abundantly expressed in cardiomyocytes during development, and is reactivated in a subset of adult cardiomyocytes after IR. Moreover, ARID1A is highly expressed in cardiomyocytes in human failing hearts, suggesting an important function in injury response. Cardiomyocyte-specific Arid1a ablation in neonatal mice induced cardiomyocyte hyperplasia, and severe cardiac enlargement at 2 weeks of age. Arid1a mutant hearts display increased expression of key cell cycle genes. Using ChIP-Seq and protein interaction studies we show that Arid1a functionally interacts with HIPPO signaling, thereby regulating neonatal cardiomyocyte proliferation. Furthermore, suppression of Arid1a in adult cardiomyocytes after IR induced cell cycle activity in border zone cardiomyocytes. These data suggest that Arid1a regulates cardiomyocyte proliferation and function. Upregulation of Arid1a in cardiomyocytes after injury may suppress proliferation and regeneration. Modulation of ARID1A after ischemic injury may be a novel therapeutic target to enhance cardiac regeneration.
2023-07-06 | GSE155101 | GEO