An increase in ROS is required for repair of the neonatal cerebellum
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE269342 | GEO | 2024/12/05
REPOSITORIES: GEO
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Project description:The inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, the neonatal mammalian heart retains a transient capacity for regeneration, which is lost shortly after birth. Defining the molecular mechanisms that govern regenerative capacity in the neonatal period remains a central goal in cardiac biology. Here, we construct a transcriptional atlas of multiple cardiac cell populations, which enables comparative analyses of the regenerative (neonatal) versus non-regenerative (adult) state for the first time. This work provides a comprehensive transcriptional resource of multiple cardiac cell populations during cardiac development, repair and regeneration. Our findings define a transcriptional program underpinning the neonatal regenerative state and identifies an epigenetic barrier to re-induction of the regenerative program in adult cardiomyocytes.
2017-07-24 | GSE95755 | 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 | 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:Background - The inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, the neonatal mammalian heart retains a transient capacity for regeneration, which is lost shortly after birth. Defining the molecular mechanisms that govern regenerative capacity in the neonatal period remains a central goal in cardiac biology. Here, we construct a transcriptional atlas of multiple cardiac cell populations, which enables comparative analyses of the regenerative (neonatal) versus non-regenerative (adult) state for the first time. Methods - Cardiomyocytes, fibroblasts, leukocytes and endothelial cells from infarcted and non-infarcted neonatal (P1) and adult (P56) hearts were isolated by enzymatic dissociation and FACS. RNA sequencing (RNA-seq) was performed on these cell populations to generate a transcriptomic atlas of the major cardiac cell populations during cardiac development, repair and regeneration. In addition, we surveyed the epigenetic landscape of cardiomyocytes during post-natal maturation by performing deep sequencing of accessible chromatin regions using the Assay for Transposase-Accessible Chromatin (ATAC-seq) from purified cardiomyocyte nuclei (P1, P14 and P56). Results - Profiling of cardiomyocyte and non-myocyte transcriptional programs uncovered several injury responsive genes across regenerative and non-regenerative time points. However, the majority of transcriptional changes in all cardiac cell types resulted from developmental maturation from neonatal stages to adulthood rather than activation of a distinct regeneration-specific gene program. Furthermore, adult leukocytes and fibroblasts reverted to a neonatal state and re-activated a neonatal proliferative network following infarction. In contrast, cardiomyocytes failed to re-activate the neonatal proliferative network following infarction, which was associated with loss of chromatin accessibility around cell cycle genes during post-natal maturation. Conclusions – This work provides a comprehensive transcriptional resource of multiple cardiac cell populations during cardiac development, repair and regeneration. Our findings define a transcriptional program underpinning the neonatal regenerative state and identifies an epigenetic barrier to re-induction of the regenerative program in adult cardiomyocytes.
2017-07-24 | GSE95763 | GEO
Project description:Background - The inability of the adult mammalian heart to regenerate following injury represents a major barrier in cardiovascular medicine. In contrast, the neonatal mammalian heart retains a transient capacity for regeneration, which is lost shortly after birth. Defining the molecular mechanisms that govern regenerative capacity in the neonatal period remains a central goal in cardiac biology. Here, we construct a transcriptional atlas of multiple cardiac cell populations, which enables comparative analyses of the regenerative (neonatal) versus non-regenerative (adult) state for the first time. Methods - Cardiomyocytes, fibroblasts, leukocytes and endothelial cells from infarcted and non-infarcted neonatal (P1) and adult (P56) hearts were isolated by enzymatic dissociation and FACS. RNA sequencing (RNA-seq) was performed on these cell populations to generate a transcriptomic atlas of the major cardiac cell populations during cardiac development, repair and regeneration. In addition, we surveyed the epigenetic landscape of cardiomyocytes during post-natal maturation by performing deep sequencing of accessible chromatin regions using the Assay for Transposase-Accessible Chromatin (ATAC-seq) from purified cardiomyocyte nuclei (P1, P14 and P56). Results - Profiling of cardiomyocyte and non-myocyte transcriptional programs uncovered several injury responsive genes across regenerative and non-regenerative time points. However, the majority of transcriptional changes in all cardiac cell types resulted from developmental maturation from neonatal stages to adulthood rather than activation of a distinct regeneration-specific gene program. Furthermore, adult leukocytes and fibroblasts reverted to a neonatal state and re-activated a neonatal proliferative network following infarction. In contrast, cardiomyocytes failed to re-activate the neonatal proliferative network following infarction, which was associated with loss of chromatin accessibility around cell cycle genes during post-natal maturation. Conclusions – This work provides a comprehensive transcriptional resource of multiple cardiac cell populations during cardiac development, repair and regeneration. Our findings define a transcriptional program underpinning the neonatal regenerative state and identifies an epigenetic barrier to re-induction of the regenerative program in adult cardiomyocytes.
2017-07-24 | GSE95762 | GEO
Project description:Paracrine effects mediated by exosomes contribute to the major regenerative functions of cell therapies after myocardial injuries. Early neonatal mammals retain a transient regeneration capacity after heart injury, which reminds us to explore the cardioprotective and regenerative potency of plasma exosomes from neonatal mouse (npEXO). Therefore, we isolated plasma exosomes from neonatal mice and performed proteomic analysis.
2022-12-13 | PXD038805 |
Project description:The regenerative capacity of the mammalian heart is lost quickly after birth when cardiomyocytes stop dividing and undergo cell cycle arrest. Thus, the adult mammalian heart lacks the ability to heal itself to any appreciable amount after ischemic injury such as myocardial infarction. Heart growth begins during fetal life with the first phase of DNA synthesis that is exclusively associated with cardiomyocyte proliferation. This process proceeds until 12 hours after birth and is defined as 0 days in our submitted samples. Cardiomyocytes division is undetectable at neonatal day 1. To analyze the molecular mechanisms responsible for cessation of cardiomyocyte proliferation, we performed genome-wide miRNA microarray profiling by comparing postnatal days 0 vs 1d.This revealed a profile of 8 significantly downregulated miRNAs in the proliferative DKO hearts (versus vehicle-injected control), that were enriched for mRNA targets involved in cell cycle regulation. In vitro studies have demonstrated that knockdown of these 8 miRNAs in neonatal rat cardiomyocytes can increase the occurrence of cytokinetic events. Ultimately, we aim to inject antagomirs targeting these miRNAs into mice post-myocardial infarction to determine the effect of these miRNAs on heart function and cardiomyocyte proliferation in vivo.
2022-01-30 | E-MTAB-9256 | biostudies-arrayexpress
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:In mammals, the neonatal heart regenerates within a short time after birth, but adults lack this ability. We have shown that metabolic reprogramming is critical for cardiomyocyte proliferation in the neonatal heart. Herein, we revealed that cardiac metabolic reprogramming could be regulated by altering global protein lactylation. 4D label-free proteomics and Kla omics were performed in postnatal Day 1 (P1), 5 (P5), and 7 (P7) mouse hearts, 2297 Kla sites from 980 proteins were identified, and 1262 Kla sites from 409 proteins were quantified. Functional clustering analysis of proteins with altered Kla sites revealed that the proteins were mainly involved in metabolic processes. The Kla levels in several fatty acid oxidation-related proteins showed high expression at P5, while glycolysis and cell cycle-related proteins were sustainedly decreased from P1-P7. Furthermore, we verified the Kla levels of several differentially modified proteins, including ACAT1, ACADL, PKM and NPM1, by coimmunoprecipitation and Western blotting. Overall, we reported the first comprehensive Kla map in the neonatal mouse heart, which will aid in understanding the regulatory network of metabolic reprogramming and cardiac regeneration.
2024-07-02 | PXD039257 | Pride