Reelin and Thrombospondin1 regulate cardiomyocyte proliferation through Vldlr
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ABSTRACT:
PROVIDER: PRJNA734577 | ENA |
REPOSITORIES: ENA
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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: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. Yap wild type ChIPseq and input
2015-02-20 | E-GEOD-57717 | biostudies-arrayexpress
Project description:Mechanical forces regulate cell behavior and tissue morphogenesis. In particular, cardiac tissues require mechanical stimuli generated by the heartbeat for differentiation and maturation, but the molecular mechanisms underlying these processes remain unclear. Here, we first show that mechanical forces acting via the mechanosensitive factor Vinculin (VCL) are essential for cardiomyocyte myofilament maturation and that cardiac contractility regulates the localization and activation of Vinculin. To further analyze the role of Vinculin in myofilament maturation, we examined its interactome in contracting cardiomyocytes and found many cytoskeletal factors including actinins. We also identified Slingshot protein phosphatase 1 (SSH1), which we show is recruited by Vinculin to regulate F-actin rearrangement and myofilament maturation through its association with the actin depolymerizing factor Cofilin (CFL). Together, our results reveal that mechanical forces generated by cardiac contractility regulate cardiomyocyte maturation through the VCL-SSH1-CFL axis, providing mechanistic insight into how mechanical forces are transmitted intracellularly to regulate myofilament maturation.
2019-09-06 | PXD014624 | Pride
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: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:Isolated adult cardiomyocytes from alpha-MHC MADM mice treated with 4 cell cycle genes to induce cardiomyocyte proliferation
2018-02-13 | GSE97729 | GEO
Project description:The goal of this study is to understand the molecular mechanisms underlying this Notch-induced muscle cell proliferation defect, we sequenced the transcriptome of control ventricles and Notch-suppressed ventricle at 5 days post-injury, when cardiomyocyte proliferation is normally robust.
2019-01-01 | GSE107228 | GEO
Project description:Endocardial Notch Signaling Promotes Cardiomyocyte Proliferation in the Regenerating Zebrafish Heart through Wnt Pathway Antagonism
| PRJNA419372 | ENA
Project description:We performed RNA-Seq analysis of neoatal rat ventricular cardiomyocytes (NRVCs) and human pluripotent stem cells derived cardiomyocytes (hPSC-CMs) which were treated with Nimodipine (NM) to investigate the moleclular mechanism of inhibiting L-type calcium channel (LTCC) to promote cardiomyocyte proliferation.
2022-10-10 | GSE185542 | 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.
2015-02-20 | GSE57718 | GEO