Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration
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ABSTRACT:
PROVIDER: PRJNA382875 | ENA |
REPOSITORIES: ENA
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Project description:Since the proliferative capacity of cardiomyocytes is extremely limited in the adult mammalian hearts, the irreversible loss of cardiomyocytes following cardiac injury markedly reduces cardiac function, leading to cardiac remodeling and heart failure. However, the early neonatal mice have a strong ability in cardiomyocyte proliferation and cardiac regeneration after heart damage such as apical resection. Besides of cardiomyocytes, non-myocytes in heart tissue also play important roles in the regeneration process. Previous studies showed that cardiac macrophages, regulatory T cells and CD4+ T cells are all involved in regulating the myocardial regeneration process. However, the roles of other cardiac immune cells in cardiac regeneration remains to be elucidated. B cells is a prominent immune cell in injured heart; here we discovered the indispensable function of cardiac B cells in improving cardiomyocyte proliferation and heart regeneration in neonatal mice.
2023-06-02 | GSE205115 | GEO
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Project description:Tp53 suppression promotes cardiomyocyte proliferation during zebrafish heart regeneration
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Project description:This SuperSeries is composed of the SubSeries listed below.
2018-02-13 | GSE97730 | GEO
Project description:To identify the potential microRNAs (miRNAs) involved in the regulation of cardiomyocyte (CM) proliferation during homeostasis and injury, RNA sequencing (RNA-seq) in mouse cardiac ventricles was performed on postnatal day 1, 7, and 28 (P1, P7, and P28). Significant upregulation of MiR-128 was found in P7 hearts as compared to P1. To further specify the effect of miR-128 in the heart, RNA-Seq was performed in control mice (Ctrl) and miR-128 overexpression mice (miR-128OE) on P7. These data provide novel insights into the mechanisms by which adult CMs exit the cell cycle arrest and is fundamental for therapeutic manipulation to stimulate endogenous CM proliferate in cardiac regeneration.
2018-01-02 | GSE107679 | GEO
Project description:To identify the potential microRNAs (miRNAs) involved in the regulation of cardiomyocyte (CM) proliferation during homeostasis and injury, RNA sequencing (RNA-seq) in mouse cardiac ventricles was performed on postnatal day 1, 7, and 28 (P1, P7, and P28). Significant upregulation of MiR-128 was found in P7 hearts as compared to P1. To further specify the effect of miR-128 in the heart, RNA-Seq was performed in control mice (Ctrl) and miR-128 overexpression mice (miR-128OE) on P7. These data provide novel insights into the mechanisms by which adult CMs exit the cell cycle arrest and is fundamental for therapeutic manipulation to stimulate endogenous CM proliferate in cardiac regeneration.
2018-01-02 | GSE107678 | GEO
Project description:Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration
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Project description:The adult mammalian heart has little regenerative capacity after myocardial infarction (MI) while neonatal mouse heart regenerates without scarring or dysfunction. However, the underlying pathways are poorly defined. We sought to derive insights into the pathways regulating neonatal development of the mouse heart and cardiac regeneration post-MI. Total RNA-seq of mouse heart through the first 10 days of postnatal life (referred to as P3, P5, P10) revealed a previously unobserved transition in microRNA expression between P3 and P5 associated specifically with altered expression of protein-coding genes on the focal adhesion pathway and cessation of cardiomyocyte cell division. We found profound changes in the coding and non-coding transcriptome after neonatal MI, with evidence of essentially complete healing by P10. Over two thirds of each of the mRNAs, lncRNAs and microRNAs that were differentially expressed in the post-MI heart were differentially expressed during normal postnatal development, suggesting a common regulatory pathway for normal cardiac development and post-MI cardiac regeneration. We selected exemplars of miRNAs implicated in our data set as regulators of cardiomyocyte proliferation. Several of these showed evidence of a functional influence on mouse cardiomyocyte cell division. In addition, a subset of these microRNAs, miR-144-3p, miR-195a-5p, miR-451a and miR-6240 showed evidence of functional conservation in human cardiomyocytes. The sets of mRNAs, miRNAs and lncRNAs that we report here merit further investigation as gatekeepers of cell division in the postnatal heart and as targets for extension of the period of cardiac regeneration beyond the neonatal period.
2018-02-02 | E-MTAB-6272 | biostudies-arrayexpress
Project description:Fibroblasts are activated to repair the heart following injury. Fibroblast activation in the mammalian heart leads to a permanent fibrotic scar that impairs cardiac function. In other organisms, such as zebrafish, cardiac injury is followed by transient fibrosis and scar-free regeneration. The mechanisms that drive scarring versus scar-free regeneration are not well understood. Here, we show that the homeobox-containing transcription factor Prrx1b is required for scar-free regeneration of the zebrafish heart as the loss of Prrx1b results in excessive fibrosis and impaired cardiomyocyte proliferation. Through lineage tracing and single-cell RNA sequencing we find that Prrx1b is activated in epicardial-derived cells where it restricts TGFβ ligand expression and collagen production. Furthermore, through combined in vitro experiments in human fetal epicardial-derived cells and in vivo rescue experiments in zebrafish, we conclude that Prrx1 stimulates Nrg1 expression and promotes cardiomyocyte proliferation. Collectively, these results indicate that Prrx1 is a key transcription factor that balances fibrosis and regeneration in the injured zebrafish heart.
2021-09-16 | GSE153170 | GEO
Project description:Loss of functional cardiomyocytes is a major determinant of heart failure after myocardial infarction. Previous high throughput screening studies have identified a series of microRNAs that induce cardiomyocyte proliferation and stimulate cardiac regeneration after myocardial infarction. Here we investigate the mechanism of action of the top ten most effective of these miRNAs. Analysis of the transcriptional profile of miRNA-treated cardiomyocytes revealed an involvement of the Hippo-YAP pathway in their action. All the investigated miRNAs activated YAP-mediated transcription, nuclear localization of active YAP and increased expression of YAP responsive genes. In particular, miR-199a-3p, one of the most effective miRNAs, directly downregulated two mRNA targets impinging on the Hippo pathway, the upstream inhibitory kinase TAOK1and the E3 ubiquitin ligase destroying YAP, b-TrCP. Most of the miRNAs that promoted proliferation also modulated the dynamics of the cardiomyocyte actin cytoskeleton. In particular, four miRNAs targeted Cofilin2 and increased the ratio between polymerized F-actin and monomeric G-actin. Cells treated with the most effective miRNAs (including miR-199a-3p) were round-shaped, with formation of gross bundles of actin fibers at the cytoplasm periphery. During mitosis, these miRNA-treated cardiomyocytes displayed disruption of the sarcomeric architecture. Downregulation of Cofilin2 itself was sufficient to promote cardiomyocyte proliferation, activate nuclear translocation of YAP and stimulate transcription of TEAD-responsive genes. Inhibition of F-actin polymerization decreased YAP activation. Collectively, these results indicate that activation of YAP and modulation of the acting cytoskeleton are major components of the pro-proliferative effect of miR-199a-3p and other miRNAs inducing cardiomyocyte proliferation
2019-04-11 | GSE129598 | GEO