Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA155869 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE35671: Comparison of mRNA expression profiling of differentiating human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes, biopsies from fetal, adult and hypertensive human hearts and primary cardiomyocytes GSE35672: miRNA expression profiling of differentiating human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes Refer to individual Series
2012-02-10 | E-GEOD-35673 | biostudies-arrayexpress
Project description:To gain insight into the molecular regulation of human heart development, a detailed comparison of the mRNA and miRNA transcriptomes across differentiating human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes and biopsies from fetal, adult, and hypertensive human hearts was performed. Gene ontology analysis of the mRNA expression levels of the hiPSCs differentiating into cardiomyocytes revealed 3 distinct groups of genes: pluripotent specific, transitional cardiac specification, and mature cardiomyocyte specific. Hierarchical clustering of the mRNA data revealed that the transcriptome of hiPSC cardiomyocytes largely stabilizes 20 days after initiation of differentiation. Nevertheless, analysis of cells continuously cultured for 120 days indicated that the cardiomyocytes continued to mature toward a more adult-like gene expression pattern. Analysis of cardiomyocyte-specific miRNAs (miR-1, miR-133a/b, and miR-208a/b) revealed a miRNA pattern indicative of stem cell to cardiomyocyte specification. A biostatistitical approach integrated the miRNA and mRNA expression profiles revealing a cardiomyocyte differentiation miRNA network and identified putative mRNAs targeted by multiple miRNAs. Together, these data reveal the miRNA network in human heart development and support the notion that overlapping miRNA networks re-enforce transcriptional control during developmental specification. Comparison of mRNA expression profiling of differentiating human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes, biopsies from fetal, adult and hypertensive human hearts and primary cardiomyocytes
2012-02-10 | E-GEOD-35671 | biostudies-arrayexpress
Project description:To gain insight into the molecular regulation of human heart development, a detailed comparison of the mRNA and miRNA transcriptomes across differentiating human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes and biopsies from fetal, adult, and hypertensive human hearts was performed. Gene ontology analysis of the mRNA expression levels of the hiPSCs differentiating into cardiomyocytes revealed 3 distinct groups of genes: pluripotent specific, transitional cardiac specification, and mature cardiomyocyte specific. Hierarchical clustering of the mRNA data revealed that the transcriptome of hiPSC cardiomyocytes largely stabilizes 20 days after initiation of differentiation. Nevertheless, analysis of cells continuously cultured for 120 days indicated that the cardiomyocytes continued to mature toward a more adult-like gene expression pattern. Analysis of cardiomyocyte-specific miRNAs (miR-1, miR-133a/b, and miR-208a/b) revealed a miRNA pattern indicative of stem cell to cardiomyocyte specification. A biostatistitical approach integrated the miRNA and mRNA expression profiles revealing a cardiomyocyte differentiation miRNA network and identified putative mRNAs targeted by multiple miRNAs. Together, these data reveal the miRNA network in human heart development and support the notion that overlapping miRNA networks re-enforce transcriptional control during developmental specification. miRNA expression profiling of differentiating human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes (days 0-120)
2012-02-10 | E-GEOD-35672 | biostudies-arrayexpress
Project description:To gain insight into the molecular regulation of human heart development, a detailed comparison of the mRNA and miRNA transcriptomes across differentiating human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes and biopsies from fetal, adult, and hypertensive human hearts was performed. Gene ontology analysis of the mRNA expression levels of the hiPSCs differentiating into cardiomyocytes revealed 3 distinct groups of genes: pluripotent specific, transitional cardiac specification, and mature cardiomyocyte specific. Hierarchical clustering of the mRNA data revealed that the transcriptome of hiPSC cardiomyocytes largely stabilizes 20 days after initiation of differentiation. Nevertheless, analysis of cells continuously cultured for 120 days indicated that the cardiomyocytes continued to mature toward a more adult-like gene expression pattern. Analysis of cardiomyocyte-specific miRNAs (miR-1, miR-133a/b, and miR-208a/b) revealed a miRNA pattern indicative of stem cell to cardiomyocyte specification. A biostatistitical approach integrated the miRNA and mRNA expression profiles revealing a cardiomyocyte differentiation miRNA network and identified putative mRNAs targeted by multiple miRNAs. Together, these data reveal the miRNA network in human heart development and support the notion that overlapping miRNA networks re-enforce transcriptional control during developmental specification.
2012-02-10 | GSE35672 | GEO
Project description:To gain insight into the molecular regulation of human heart development, a detailed comparison of the mRNA and miRNA transcriptomes across differentiating human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes and biopsies from fetal, adult, and hypertensive human hearts was performed. Gene ontology analysis of the mRNA expression levels of the hiPSCs differentiating into cardiomyocytes revealed 3 distinct groups of genes: pluripotent specific, transitional cardiac specification, and mature cardiomyocyte specific. Hierarchical clustering of the mRNA data revealed that the transcriptome of hiPSC cardiomyocytes largely stabilizes 20 days after initiation of differentiation. Nevertheless, analysis of cells continuously cultured for 120 days indicated that the cardiomyocytes continued to mature toward a more adult-like gene expression pattern. Analysis of cardiomyocyte-specific miRNAs (miR-1, miR-133a/b, and miR-208a/b) revealed a miRNA pattern indicative of stem cell to cardiomyocyte specification. A biostatistitical approach integrated the miRNA and mRNA expression profiles revealing a cardiomyocyte differentiation miRNA network and identified putative mRNAs targeted by multiple miRNAs. Together, these data reveal the miRNA network in human heart development and support the notion that overlapping miRNA networks re-enforce transcriptional control during developmental specification.
2012-02-10 | GSE35671 | GEO
Project description:Mitochondria play a crucial role in the differentiation and maturation of human cardiomyocytes (CMs). To identify mitochondrial pathways and regulators that are involved in cardiac differentiation and maturation, we examined human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Proteomic analysis was performed on enriched mitochondrial protein extracts isolated from hiPSC-CMs differentiated from dermal fibroblasts (dFCM) and cardiac fibroblasts (cFCM), at different days of differentiation (between 12 and 115 days), and also from adult and neonatal mouse hearts for comparison. Mitochondrial proteins with a ≥2-fold change between differentiation time points in dFCMs and cFCMs, and between adult versus neonatal mouse hearts, were subjected to Ingenuity Pathway Analysis (IPA), and some upregulated proteins were validated by immunoblotting. The highest significant upregulation was in metabolic pathways for fatty acid oxidation (FAO), the tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS) and branched chain amino acid (BCAA) catabolism. The top upstream regulators predicted by IPA were- peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1-a), the insulin receptor and the retinoblastoma protein (Rb) transcriptional repressor. In addition, IPA and immunoblotting showed substantial upregulation of the mitochondrial LonP1 protease, which regulates mitochondrial proteostasis, energetics and metabolism. Using this proteomics approach, we have identified key metabolic and intracellular signaling pathways that are up- and down- regulated during the biogenesis of mitochondria in differentiating and maturing cardiac myocytes.
2022-05-19 | PXD014317 | Pride
Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are used to examine in vitro the effect of mutations in the cardiac sodium channel gene SCN5A, associated with cardiac arrhythmias. Postnatally SCN5A undergoes a fetal-to-adult isoform switch, but hiPSC-CMs in conventional 2-dimensional cultures are fetal-like. This impedes evaluation of mutations in the adult isoform. Here, we derived hiPSC-CMs from a patient carrying compound mutations in the adult SCN5A exon 6B and in exon 4 and generated isogenic corrected lines. In hiPSC-CM 2-dimensional culture, exon 6B mutation did not affect single-cell electrophysiology because of its limited expression. CRISPR/Cas9-mediated excision of the fetal exon 6A with did not promote adult SCN5A expression, rather it impaired the splicing. By maturing hiPSC-CMs in three-dimensional tri-cell type cardiac microtissues, SCN5A underwent isoform switch and revealed the functional effect of exon 6B mutation. Upregulation of the splicing factor MBNL1 in hiPSC-CMs either by culture in microtissues or by overexpression was sufficient to promote exon 6B inclusion. Our results support the ability to study developmentally regulated cardiac genes and postnatal cardiac arrhythmias using hiPSC cardiac cells.
2023-05-03 | GSE180290 | GEO
Project description:miRNA expression profiling of differentiating human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes
| PRJNA155871 | ENA
Project description:Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide great opportunities for mechanistic dissection of human cardiac pathophysiology; however, hiPSC-CMs remain immature relative to the adult heart. To identify novel signaling pathways driving the maturation process during heart development, we analyzed published transcriptional and epigenetic datasets from hiPSC-CMs, prenatal and postnatal human hearts. These analyses revealed that several components of the MAPK and PI3K-AKT pathways are downregulated in the postnatal heart. Here, we show that dual inhibition of these pathways for only 5 days significantly enhances the maturation of day-30 hiPSC-CMs in many domains: hypertrophy, multinucleation, metabolism, t-tubule density, calcium handling, and electrophysiology, many equivalent to day-60 hiPSC-CMs. These data indicate that the MAPK/PI3K/AKT pathways are involved in cardiomyocyte maturation and provide proof-of-concept for the manipulation of key signaling pathways for optimal hiPSC-CM maturation, a critical aspect of faithful in vitro modeling of cardiac pathologies and subsequent drug discovery.
2022-08-04 | GSE187308 | GEO