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Accession IconSRP075977

Transcriptome signatures of human induced pluripotent stem cell-derived cardiomyocytes classify cardiomyocyte subtype populations

Organism Icon Homo sapiens
Sample Icon 38 Downloadable Samples
Technology Badge IconIllumina HiSeq 2000

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Description
We profiled the transcriptome of cardiomyocytes from hiPSCs throughout differentiation and at a single cell level to identify subpopulations. We further studied on the transcription factors NR2F2, TBX5, and HEY2 in these subpopulations. Overall design: Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) have become a powerful tool for human disease modeling and therapeutic testing. However, their use remains limited by their immaturity and heterogeneity. To characterize the source of this heterogeneity, we performed bulk RNA-seq on hiPSCs undergoing differentiation into cardiomyocytes over an extended time course followed by single-cell RNA-seq at a later time point (day 30). These analyses identified novel single-cell populations, characterized by the distinct or overlapping expression of TBX5, NR2F2, HEY2, ISL1, JARID2, and HOPX transcription factors. Analysis of RNA-seq data from hiPSC-CMs both during differentiation in vitro and from human heart tissues suggests these transcription factors underlie physiologically distinct lineages. Using CRISPR genome editing and ChIP-seq, in conjunction with patch clamp, calcium imaging, CYTOF, and single-cell Western analysis, we now demonstrate that these transcription factors play an essential role in specification of early atrial (NR2F2) and late ventricular (HEY2) cardiomyocytes. We RNA-sequenced NR2F2, TBX5, HEY2 gene edited lines as well as day 30 hiPSC-CMs overexpressing NR2F2, TBX5, and HEY2. These new targets, sequencing data, and methods provide a platform for improved investigation of in vitro cardiac heterogeneity.
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39
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