Similar Datasets
Project description:hiPS derived cardiomycoytes treated with 4 cell cycle genes to induce cardiomyocyte proliferation and sorted for the different cell cycle stages according to FUCCI dye
2018-02-13 | GSE97728 | GEO
Project description:Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac function. However, the role of metabolism in different aspects of cardiomyocyte regeneration remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), especially in tissues bordering the damaged area. We further find that impaired glycolysis decreases the number of proliferating cardiomyocytes following injury. These observations are supported by analyses using loss-of-function models for the metabolic regulators Pkma2 and peroxisome proliferator-activated receptor gamma coactivator 1 alpha. Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 as well as a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation after injury. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.
2020-07-13 | PXD016235 | Pride
Project description:The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation. However, this regenerative capacity is lost by postnatal (P) day 7. How to stimulate the adult cardiomyocyte to re-enter the cell cycle is still unknown. Accumulating evidence suggests that cardiomyocyte proliferation depends on its metabolic state. Due to the tight connection between the tricarboxylic acid cycle (TCA) and cell proliferation, we analyzed the TCA metabolites between P0.5 and P7 mouse hearts and found that α-ketoglutarate (α-KG) ranked first among the decreased metabolites. The intraperitoneal injection of exogenous α-KG extended the window of cardiomyocyte proliferation during heart development and promoted heart regeneration after myocardial infarction (MI) by inducing adult cardiomyocyte proliferation. This was confirmed in Ogdh-siRNA-treated mice with increased α-KG levels. Mechanistically, α-KG activates Jmjd3, a histone lysine demethylase, that decreases H3K27me3 expression and deposition of H3K4me3 at the promoters of cell cycle and structural maturation genes in cardiomyocytes. Our present study shows that α-KG promotes cardiomyocyte proliferation by Jmjd3-dependent demethylation and inactivation of H3K27me3 andH3K4me3, which is a potential therapeutic approach for treating MI and heart failure.
2024-07-12 | GSE272104 | GEO
Project description:A recent study suggests that systemic hypoxemia in adult male mice can induce cardiac myocytes to proliferate. The goal of the present experiments was to confirm these results, provide new insights on the mechanisms that induce adult cardiomyocyte cell cycle re-entry, and to determine if hypoxemia also induces cardiomyocyte proliferation in female mice. We also analyzed gene expression using data obtained from RNAseq of ventricular heart tissue from male and female mice subjected to either normoxia or hypoxia.
2023-02-15 | GSE221168 | GEO
Project description:We performed RNA-Seq analysis of neoatal rat ventricular cardiomyocytes (NRVCs)which were treated with Reelin,or knocking down Vldlr,Thbs1,or overexpressing Vldlr to investigate the moleclular mechanism of Thbs1/Reelin-Vldlr to regulate cardiomyocyte proliferation.In addition,the day 1mouse cardiomyocytes in Myh6-Cre;Vldlr f/f mice ,Myh6-Cre;Vldlr f/+ mice ,versus Vldlr f/f mice were also performed to explore the fucntion of Vldlr which regulating cardiomyocyte proliferation in vivo.
2021-06-03 | GSE176009 | GEO
Project description:The differentiation to cardiomyocytes is a prerequisite and an important part of heart development. A good understanding of the complicated cardiomyocyte differentiation process benefits cardiogenesis study. Embryonic stem cells (ESCs), cell lines with infinite ability to proliferate and to be differentiated into all cell types of the adult body, are important research tools for investigation of differentiation and meanwhile good models for developmental research. In the current study, genome-wide gene expression of ESCs is profiled through high throughput platform during cardiomyocyte-specific differentiation and maturation. Gene expression patterns of undifferentiated ESCs and ESC-derived cardiomyocytes provide a global overview of genes involved in cardiomyocyte-specific differentiation, whereas marker gene expression profiles of both ESC-related genes and cardiac-specific genes presented the expression pattern shift during differentiation in a pure ESC-derived cardiomyocyte cell culture system. Transgenic mouse ESC clone with M-NM-1-MHCM-bM-^@M-^SPacM-bM-^@M-^SIRESM-bM-^@M-^SEGFP vector containing the EGFP gene and the PuromycinR (Pac) cassette under control of the cardiac M-NM-1-myosin heavy chain (M-NM-1-MHC) promoter was cultured and induced into differentiation. Puromycin was applied after differentiation start to enable cardiomyocyte-specific differentiation. Cells were harvested at 4 time points after differentiation start (day0, day12, day19 and day26). Two biological replicates were taken for every time point.
2014-09-25 | E-GEOD-58300 | biostudies-arrayexpress
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
Project description:Cardiac metabolism plays a crucial role in producing sufficient energy to sustain cardiac contractions. However, the role of metabolism in cardiomyocyte proliferation remains unclear. Working with the adult zebrafish heart regeneration model, we first find an increase in the levels of mRNAs encoding enzymes regulating glucose and pyruvate metabolism, including pyruvate kinase M1/2 (Pkm) and pyruvate dehydrogenase kinases (Pdks), specifically in tissues bordering the damaged area. We proceed to show that impaired glycolysis decreases the number of proliferating cardiomyocytes following cardiac injury. These observations are further supported by analyses using loss-of-function models for the metabolic regulators Pkm2a and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Ppargc1a). Cardiomyocyte-specific loss- and gain-of-function manipulations of pyruvate metabolism using Pdk3 and a catalytic subunit of the pyruvate dehydrogenase complex (PDC) reveal its importance in cardiomyocyte dedifferentiation and proliferation. Furthermore, we find that PDK activity can modulate cell cycle progression and protrusive activity in mammalian cardiomyocytes in culture. Our findings reveal new roles for cardiac metabolism and the PDK-PDC axis in cardiomyocyte behavior following cardiac injury.
2020-06-04 | GSE147073 | GEO
Project description:Background—YAP, the nuclear effector of Hippo signaling, regulates cellular growth and survival in multiple organs, including the heart, by interacting with TEAD sequence specific DNA-binding proteins. Recent studies showed that YAP stimulates cardiomyocyte proliferation and survival. However, the direct transcriptional targets through which YAP exerts its effects are poorly defined. Methods and Results—To identify genes directly regulated by YAP in cardiomyocytes, we combined differential gene expression analysis in YAP gain- and loss-of-function with genome-wide identification of YAP bound loci using chromatin immunoprecipitation and high throughput sequencing. This screen identified Pik3cb, encoding p110β, a catalytic subunit of phosphoinositol-3-kinase (PI3K), as a candidate YAP effector that promotes cardiomyocyte proliferation and survival. We validated YAP and TEAD occupancy of a conserved enhancer within the first intron of Pik3cb, and show that this enhancer drives YAP-dependent reporter gene expression. Yap gain- and loss-of-function studies indicated that YAP is necessary and sufficient to activate the PI3K-Akt pathway. Like Yap, Pik3cb gain-of-function stimulated cardiomyocyte proliferation, and Pik3cb knockdown dampened the YAP mitogenic activity. Reciprocally, Yap loss-of-function impaired heart function and reduced cardiomyocyte proliferation and survival, all of which were significantly rescued by AAV-mediated Pik3cb expression. Conclusion—Pik3cb is a crucial direct target of YAP, through which the YAP activates PI3K-AKT pathway and regulates cardiomyocyte proliferation and survival. Two groups were involved in this study:TNTcreYapfl_het group and TNTcreYapfl_KO group. Each group contained three biological replicates. Embryo hearts were collected at E12.5 and dissociated. Cardiomyocytes were collected by FACS. The total RNA of cardiomyocytes were isolated for microarray analysis.
2015-02-20 | E-GEOD-57718 | biostudies-arrayexpress
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