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
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)
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
Project description:To investigate the changes in gene profiles during the long-term culture process of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes, we conducted microarray analysis on hiPSC(253G4 line)- derived cardiomyocytes at three time points: 20 days, 35 days, and 50 days after the initiation of differentiation induction.
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.
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.
Project description:Here we developed a novel human induced pluripotent stem cell (hiPSC) model of ARVC to gain insight into the electrical and biomolecular effects of desmoglein-2 (DSG2) mutation in cardiomyocytes. hiPSC-derived cardiomyocytes (hiPSC-CMs) were generated from peripheral blood mononuclear cells donated by an ARVC patient with a pathogenic variant in DSG2, c.2358delA.
Project description:In this study, we employed an inducible CRISPRi human induced pluripotent stem cell (hiPSC) line to silence TERT expression enabling the generation of hiPSCs and hiPSC-derived cardiomyocytes with long and short telomeres. Reduced telomerase activity and shorter telomere lengths of hiPSCs strongly hampered their differentiation potential towards cardiomyocytes
Project description:Previously, we reported upregulation of cardiac proliferation in cardiac progenitors derived from human induced pluripotent stem cells (hiPSC-CPCs) that were exposed to space microgravity for 3 days. The overall objective of this investigation was to understand how long-term exposure to microgravity affects the expansion and differentiation of hiPSC-CPCs. Cryopreserved cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) were exposed to space microgravity for 3 weeks in the International Space Station (ISS) and retrieved for transcriptomic profiling. RNA-seq analysis and gene ontology analysis revealed upregulation of cardiac tissue function and morphological terms while downregulating inflammation and ECM regulation terms. Upregulation of genes associated with cell cycle regulation and proliferation were notable as well. Combined with previous work, these results suggest that space microgravity improved cardiac differentiation and structure formation and potentially, proliferation.