Analysis of transcrptomes of Danon patient derived hiPSC-cardiomyocytes by RNA-deep Sequencing
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE108429 | GEO | 2018/12/11
REPOSITORIES: GEO
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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:Human embryonic and induced pluripotent stem cells (hESCs/iPSCs) are promising cell sources for cardiac regenerative medicine. To realize hESC/iPSC-based cardiac cell therapy, efficient induction, purification, and transplantation methods for cardiomyocytes should be required. Though marker gene transduction or fluorescent-based purification methods were reported, fast, efficient and scalable purification methods with no genetic modification are essential for clinical purposes but have not been established yet. In this study, we used microarrays to detail the global gene program during cardiac differentiation and to identify cardiac-specific cell surface markers. hiPSCs (201B6) were differentiated toward cardiomyocytes using a modified-directed differentiation protocol (high density culture in RPMI+B27-insulin, sequential administration of Activin A 100ng/mL 1 day, BMP4 10ng/mL+bFGF 10ng/mL 4 days, and Dkk1 100ng/mL 2 days). Beating clusters were first observed at day 8-9 and spread by day 11 after Activin A administration. Cardiac troponin-T (cTnT)-positive cells appeared at day 7-8 after induction and were observed in 30-70% of cells at day 11. qPCR and genome-wide analysis reflected differentiation processes from the undifferentiated state to cardiomyocytes. Rapid downregulation of pluripotent stem cell markers such as NANOG and POU5F1 was observed within 2 days of differentiation. Early and cardiac mesodermal genes (T, MESP1, KDR, ISL1) were expressed during day 2-5, and cardiac genes (NKX2-5, MYH6, MYH7, MYL2, and MYL7) were expressed after day 7. We identified VCAM1 as a cardiac-specific cell surface marker by microarray and flow cytometry. Human induced pluripotent stem cells (iPSCs; 201B6) were differentiated toward cardiomyocytes (RPMI+B27 medium supplemented d0-1 Activin A, d1-5 BMP4+bFGF, d5-7 Dkk1). RNA was extracted from cells at day 0, day 2, day 5, day 7, day 9, and day 11. Cardiomyocytes appeared after day 7 and reached about 50% of total cells at day 11.
2011-12-31 | E-GEOD-28191 | biostudies-arrayexpress
Project description:Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the âageâ of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia SZ generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SZ brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SZ might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SZ patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SZ hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes and WNT signaling. Methods: We compared global transcription of forebrain NPCs from six control and four SZ patients by RNAseq. Results: Multi-dimensional scaling (MDS) resolved most SZ and control hiPSC NPC samples; 848 genes were significantly differentially expressed (FDR<0.01) Conclusions: The WNT signaling pathway was enriched 2-fold (fisher exact test p-value = 0.031). 1-2 independent differentiations (biological replicates) for each of four control and four schizophrenia patients were analyzed; samples were generated in parallel to neuron RNAseq data.
2016-03-14 | E-GEOD-63738 | biostudies-arrayexpress
Project description:Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia SZ generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SZ brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus. We directly reprogrammed fibroblasts from SZ patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into forebrain neurons. SZ hiPSC differentiated into forebrain neurons have altered expression of a number of synaptic genes. Methods: We compared global transcription of forebrain neurons from six control and four SZ patients by RNAseq. Results: Multi-dimensional scaling (MDS) resolved most SZ and control hiPSC neuron samples; 107 genes were significantly differentially expressed (FDR<0.01)
2016-04-21 | GSE63734 | GEO
Project description:Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia SZ generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SZ brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SZ might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SZ patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SZ hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes and WNT signaling. Methods: We compared global transcription of forebrain NPCs from six control and four SZ patients by RNAseq. Results: Multi-dimensional scaling (MDS) resolved most SZ and control hiPSC NPC samples; 848 genes were significantly differentially expressed (FDR<0.01) Conclusions: The WNT signaling pathway was enriched 2-fold (fisher exact test p-value = 0.031).
2016-03-14 | GSE63738 | GEO
Project description:Directed differentiation methods allow acquisition of high-purity cardiomyocytes (CMs) differentiated from human induced pluripotent stem cells (hiPSCs); however, their immaturity characteristic limits their application for drug screening and regenerative therapy. The rapid electrical pacing of cardiomyocytes have been used for efficiently promoting the maturation of cardiomyocytes, here we describe a simple device in modified culture plate on which hiPSC-derived CMs can form three-dimensional self-organized tissue rings (SOTRs). Using calcium imaging, we show that within the ring, traveling waves (TWs) of action potential spontaneously originated and ran robustly at a frequency up to 4 Hz. After 2 weeks, SOTRs with TW training show matured features including structural organization, increased cardiac-specific gene expression, enhanced Ca2+-handling properties, an increased oxygen-consumption rate, and enhanced contractile force. We subsequently use a mathematical model to interpret the origination, propagation, and long-term behavior of the TWs within the SOTRs. The TW could also potentially be used for pacing the electrical excitable cells such as neuron and retina cells for various applications.
2020-02-05 | GSE140466 | 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. 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.
2012-02-10 | GSE35672 | GEO
Project description:We cultured differentiated hiPSC-derived cardiomyocytes either alone or in co-culture with hiPSC-derived endothelial cells to evaluate potential genes that might facilitate endothelial cell-mediated cardiomyocyte maturation.
2023-03-08 | GSE210513 | GEO
Project description:Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia (SCZD) generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SCZD brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SCZD might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SCZD patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SCZD hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes, reduced WNT signaling and aberrant cellular migration. 3 independent differentiations (biological replicates) for each of four control and four schizophrenic patients were analyzed.
2014-04-01 | E-GEOD-40102 | biostudies-arrayexpress