Cardiac differentiation of human pluripotent stem cells (hPSCs) requires orchestration of dynamic gene regulatory networks during stepwise fate transitions but often generates immature cell types that do not fully recapitulate properties of their adult counterparts, suggesting incomplete activation of key transcriptional networks. We performed extensive single-cell transcriptomic analyses to map fate choices and gene expression programs during cardiac differentiation of hPSCs and identified strategies to improve in vitro cardiomyocyte differentiation. Utilizing genetic gain- and loss-of-function approaches, we found that hypertrophic signaling is not effectively activated during monolayer-based cardiac differentiation, thereby preventing expression of HOPX and its activation of downstream genes that govern late stages of cardiomyocyte maturation. This study therefore provides a key transcriptional roadmap of in vitro cardiac differentiation at single-cell resolution, revealing fundamental mechanisms underlying heart development and differentiation of hPSC-derived cardiomyocytes.
Pubmed ID: 30290179 RIS Download
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International functional genomics data collection generated from microarray or next-generation sequencing (NGS) platforms. Repository of functional genomics data supporting publications. Provides genes expression data for reuse to the research community where they can be queried and downloaded. Integrated with the Gene Expression Atlas and the sequence databases at the European Bioinformatics Institute. Contains a subset of curated and re-annotated Archive data which can be queried for individual gene expression under different biological conditions across experiments. Data collected to MIAME and MINSEQE standards. Data are submitted by users or are imported directly from the NCBI Gene Expression Omnibus.
View all literature mentionsSoftware package for low-level analyses of single-cell RNA-seq data. Used for quality control, data exploration and normalization, cell cycle phase assignment, identification of highly variable and correlated genes, clustering into subpopulations and marker gene detection.
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View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
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View all literature mentionsThis monoclonal targets Human APJ Allophycocyanin MAb (Clone 72133)
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View all literature mentionsThis polyclonal secondary targets IgG (H+L)
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View all literature mentionsCell line WTC CRISPRi HOPX g4 is a Induced pluripotent stem cell with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line CRISPRi Gen1C 5 is a Induced pluripotent stem cell with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line WTC11 HOPX-NLS-eGFP is a Induced pluripotent stem cell with a species of origin Homo sapiens (Human)
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View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsSoftware tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsCell line WTC11 NLS-eGFP is a Induced pluripotent stem cell with a species of origin Homo sapiens (Human)
View all literature mentionsCell line WTC CRISPRi HOPX g1 is a Induced pluripotent stem cell with a species of origin Homo sapiens (Human)
View all literature mentionsCell line WTC11 HOPX-NLS-eGFP is a Induced pluripotent stem cell with a species of origin Homo sapiens (Human)
View all literature mentionsCell line WTC CRISPRi HOPX g4 is a Induced pluripotent stem cell with a species of origin Homo sapiens (Human)
View all literature mentionsCell line CRISPRi Gen1C 5 is a Induced pluripotent stem cell with a species of origin Homo sapiens (Human)
View all literature mentionsCell line RUES2 HOPX KO is a Embryonic stem cell with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets Rabbit IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets DsRed
View all literature mentionsCell line RUES2 HOPX-tdTomato is a Embryonic stem cell with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets Goat Mouse IgG (H L)-HRP Conjugate
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets Human APJ Allophycocyanin MAb (Clone 72133)
View all literature mentionsThis monoclonal targets Cardiac Troponin T
View all literature mentionsThis monoclonal targets alpha-Actinin (Sarcomeric)
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets alpha-Tubulin
View all literature mentions