PITX2-KO_hiPSC_snRNAseq
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ABSTRACT:
PROVIDER: PRJEB75160 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To identifycandidate PITX2-dependent genes during corneal development, microarray analysis was used to profile gene expression in corneas taken from flash-frozen e12.5 mouse embryos of control (Pitx2+/-) and temporal knockout Pitx2-deficient embryos.
2016-12-01 | GSE76047 | GEO
Project description:Pitx2 is the homeobox gene located in proximity to the human 4q25 familial atrial fibrillation locus. Pitx2 haploinsufficient mice are prone to pacing induced atrial fibrillation indicating that reduced Pitx2 promotes an arrhythmogenic substrate within the atrium. Here, we inactivated Pitx2 in postnatal heart and discovered that unstressed adult Pitx2 mutant mice had sinus node dysfunction with impaired atrial conduction, an arrhythmia closely associated with atrial fibrillation. A genome-wide search for Pitx2 transcriptional targets using ChIP-sequencing and RNA expression profiling shows that Pitx2 represses target genes encoding cell junction proteins, ion channels, and critical transcriptional regulators many of which have been implicated in human atrial fibrillation by genome wide association studies. Pitx2 control and mutant hearts were collected from 3-, 6- and 12-week-old mice. At each time point, three cotrols and three mutants were collected as biological replicates. cDNA microarray analysis was performed using Affymetrix GeneChip Mouse Genome 430 2.0 Array (Affymetrix, Santa Clara, CA).
2014-02-01 | E-GEOD-50399 | biostudies-arrayexpress
Project description:Pitx2 is the homeobox gene located in proximity to the human 4q25 familial atrial fibrillation locus. Pitx2 haploinsufficient mice are prone to pacing induced atrial fibrillation indicating that reduced Pitx2 promotes an arrhythmogenic substrate within the atrium. Here, we inactivated Pitx2 in postnatal heart and discovered that unstressed adult Pitx2 mutant mice had sinus node dysfunction with impaired atrial conduction, an arrhythmia closely associated with atrial fibrillation. A genome-wide search for Pitx2 transcriptional targets using ChIP-sequencing and RNA expression profiling shows that Pitx2 represses target genes encoding cell junction proteins, ion channels, and critical transcriptional regulators many of which have been implicated in human atrial fibrillation by genome wide association studies. Our findings unveil a Pitx2 postnatal arrhythmogenic function, novel Pitx2 target genes relevant to atrial fibrillation, and reveal that Pitx2 stabilizes the intercalated disc in postnatal atrium.
2014-02-01 | GSE47928 | GEO
Project description:Introduction: Atrial fibrillation (AF) is the most common arrhythmia and affects around 1% of the population with increasing incidence and substantial morbidity. Functional effects of genetic variants associated with AF should help to identify targets involved in AF initiation and/or subsequent remodeling. Gene variants next to the gene of the transcription factor PITX2 (paired-like homeodomain transcription factor 2) showed the strongest association with AF. A significant number of AF patients showed reduced PITX2 levels in the left atrium. Mouse models have been used to study functional aspects of PITX2 gene deletion (“knock out”), but there are substantial differences in atrial electrophysiology between mouse and human . HiPSC-CM should be able to bridge the gap, provided the cells reproduce typical characteristics of human atrium. Methods: PITX2 knock out samples from a control cell line of human induced pluripotent stem cells (hiPSC) were obtained. Differentiation and generation of Atrial-like engineered heart tissue (aEHT) was performed. RNA-sequencing (RNA-Seq), Quantitative Real-time PCR (RT-qPCR), Protein analysis by Western Blot, Contraction and force analysis, action potential measurements, Calcium current measurements and differential gene expression analysis were run on the samples. Results: Effective knock out of PITX2 was confirmed by mRNA sequencing and WB. It was shown that PITX2 deficiency reduces contraction force. PITX2 deficiency induces action potential triangulation with more negative maximum diastolic potential. Activation of muscarinic receptors shortens APD in both PITX2 knockout and controls but hyperpolarization is lost in PITX2 knock out. It was shown that Ca2+ current density is smaller in PITX2 knock out than controls. We found that more negative MDP in PITX2 knock out is not associated with higher IK1. Conclusion: We improved atrial differentiation, coming very close to human atrial electrophysiology. We demonstrate that PITX2 deficiency induces key characteristics known from persistent AF.
2024-05-31 | GSE175944 | GEO
Project description:Here, we performed single nuclear RNA-seq (snRNA-seq) of control and Pitx2 deficient cardiac tissue 3 weeks post myocardial infarction. Next, unsupervised graph-based clustering of the combined snRNA-Seq data set mapped to both introns and exons, comprising 7848 cells. Overall, we identified nine transcriptionally distinct clusters representing all the major cardiac cell types, including cardiac fibroblasts (FB), cardiomyocytes (CM), endothelial cells (EC), vascular smooth muscle cells (SMC), macrophages (Mφ), epicardial cells (EpiC), endocardial cells (EndoC), lymphatic endothelial cells (LEC), and mural cells or pericytes (PeC). Moreover, two distinct populations of fibroblasts, designated FB-1 and FB-2, were also identified.
2018-08-26 | GSE117893 | GEO
Project description:Pitx2 is the homeobox gene located in proximity to the human 4q25 familial atrial fibrillation locus. Pitx2 haploinsufficient mice are prone to pacing induced atrial fibrillation indicating that reduced Pitx2 promotes an arrhythmogenic substrate within the atrium. Here, we inactivated Pitx2 in postnatal heart and discovered that unstressed adult Pitx2 mutant mice had sinus node dysfunction with impaired atrial conduction, an arrhythmia closely associated with atrial fibrillation. A genome-wide search for Pitx2 transcriptional targets using ChIP-sequencing and RNA expression profiling shows that Pitx2 represses target genes encoding cell junction proteins, ion channels, and critical transcriptional regulators many of which have been implicated in human atrial fibrillation by genome wide association studies. Our findings unveil a Pitx2 postnatal arrhythmogenic function, novel Pitx2 target genes relevant to atrial fibrillation, and reveal that Pitx2 stabilizes the intercalated disc in postnatal atrium. Genomic occupancy profiling of transcriptional factor Pitx2 in postnatal heart.
2014-02-01 | E-GEOD-47928 | biostudies-arrayexpress
Project description:Pitx2 is the homeobox gene located in proximity to the human 4q25 familial atrial fibrillation locus. Pitx2 haploinsufficient mice are prone to pacing induced atrial fibrillation indicating that reduced Pitx2 promotes an arrhythmogenic substrate within the atrium. Here, we inactivated Pitx2 in postnatal heart and discovered that unstressed adult Pitx2 mutant mice had sinus node dysfunction with impaired atrial conduction, an arrhythmia closely associated with atrial fibrillation. A genome-wide search for Pitx2 transcriptional targets using ChIP-sequencing and RNA expression profiling shows that Pitx2 represses target genes encoding cell junction proteins, ion channels, and critical transcriptional regulators many of which have been implicated in human atrial fibrillation by genome wide association studies.
2014-02-01 | GSE50399 | GEO
Project description:PITX2 is a homeodomain transcription factor that has a substantial role in cell proliferation and differentiation in various tissues. In this study we have characterized PITX2-regulating genes. These data provide an insightful perspective for further studying PITX2 function and mechanism of action.
2008-12-31 | GSE13216 | GEO
Project description:Myocardial infarction results in compromised myocardial function with heart failure due to insufficient cardiomyocyte self-renewal. Unlike lower vertebrates, mammalian hearts only have a transient neonatal renewal capacity. Reactivating the primitive reparative ability in the fully mature heart requires an intimate knowledge of the molecular mechanisms promoting early heart repair. Here we identified a novel factor that can sufficiently promote heart muscle repair. By screening an established Hippo-deficient heart regeneration model for renewal promoting factors, we found that PITX2 protein expression in ventricles was induced after cardiomyocyte injury. Moreover, Pitx2-deficient neonatal hearts failed to repair after apex resection. Pitx2-gain-of-function in ventricular cardiomyocytes conferred reparative ability to the adult mouse heart after myocardial infarction. Integrated genomic analyses indicated that Pitx2 activated genes encoding electron transport chain components and reactive oxygen species scavengers. Pitx2 mutant myocardium had elevated reactive oxygen species levels while supplement of antioxidants suppressed the Pitx2-loss-of-function phenotype. Furthermore, PITX2 directly binds NFE2L2 and translocates from cytoplasm to nucleus upon oxidative stress.
2016-05-19 | GSE70413 | GEO
Project description:To identify genes whose expressions in primary human trabecular meshwork (TM) cell cultures are affected by the transcription factor PITX2 and to identify genes that may have roles in glaucoma. Expression profiles derived using microarrays were compared between TM control cells and cells treated with PITX2 siRNAs
2011-04-01 | GSE27275 | GEO