Project description:Here we provide the gene expression patterns of human iPS cell-derived cardiomyocytes used in the motion field imaging assay, adult human heart tissues, fetal human heart tissue and iPS cells. These data provided the causal relationship between phenotype and function in the human iPS cell-derived cardiomyocytes.
Project description:Analysis of human iPS-derived cardiomyocytes exposed to glucose, endothelin-1 and cortisol in vitro. Treatment produces a surrogate diabetic cardiomyopathic phenotype. Results provide insight into the pathways regulated by the treatment in the cardiomyocyte. The RNA for each vehicle-control treated and glucose endothelin cortisol treated iPS derived cardiomyocytes from 4 replicate samples, were extracted and hybridized to 8 individual human HG-U133 Plus2.0 Affymetrix microarray gene chips, whereby each chip represented the expression profile for one cell culture at 2 days.
Project description:Gene expression profile of endothelin-1 (ET-1) stressed human derived iPS cardiomyocytes (from Cellular Dynamics) with or without the BET bromodomain inhibitor JQ1
Project description:We report the effect of the deletion of STK25 kinase on the transcriptomes of induced pluripotent stem cell derived cardiomyocytes (iPS-CM).
Project description:Recent establishment of induced pluripotent stem (iPS) cells opened new avenues for generating human patient-specific stem cell derivatives that can be used for in vitro modeling of human disease, drug development and cell replacement therapy. In this study we analyzed the molecular and functional properties of cardiomyocytes (CM) differentiated from human iPS cells. Clusters of synchronously beating cells were first observed at day 11 of iPS cell differentiation. Beating clusters that were microdissected at day 18 of differentiation expressed high levels of cardiospecific transcripts NKx2.5, alpha-MHC, MLC2v, alpha-actinin and troponin T. Immunocytochemical stainings for alpha-actinin and troponin T revealed cross-striations typical of CM. Functional assessment of iPS cell-derived CM showed that these cells possess intact calcium transients and respond to beta-adrenergic and muscarinic stimulation. Molecular, structural and electrophysiological properties of iPS cell-derived CMs were highly comparable to their human ES cell-derived counterparts at the same differentiation stage. Comparison of global gene expression profiles of human ES and iPS cells and the corresponding microdissected beating areas further confirmed their similarity. We conclude that human iPS cells can differentiate into functional CM, which are indistinguishable from human ES cell-derived CMs and may fulfill the basic requirement for their use in disease modeling, drug screening and future therapeutic applications. Six different experimental groups were included into analysis: undifferentiated human ES cells (1) and undifferentiated human iPS cells (2), human ES cell-derived cardiomyocytes (3) and human iPS cell-derived cardiomyocytes (4) enriched by microdissection of spontaneously contracting embryoid body outgrowths, and human fetal (5) and adult (6) heart tissue. Total RNA samples were prepared from three independent biological replicates in groups 1-4. In groups 5 and 6, single RNA probes were analyzed as three technical replicates.
Project description:Drug-induced cardiac arrhythmia characterized by QT prolongation and torsade de pointes has been a major reason for drug withdrawal at the late stage of clinical trials. Current preclinical testing is still insufficient to identify drugs with pro-arrhythmic risks. Human induced pluripotent stem cell-derived cardiomyocytes are a promising development in safety screening as a reproducible human model. Using the patch-clamp technique, we showed that human induced pluripotent stem cell-derived cardiomyocytes exhibited spontaneous action potentials, which represent relatively immature forms of cardiac cells. Furthermore, in some spontaneously beating cells, a hERG blocker, E4031, depolarized membrane potentials and stopped spontaneous firing, resulting in failure to evaluate drug effects on electrophysiological parameters that reflect repolarization processes. Here we show that human stem cell-derived cardiomyocytes with transduced KCNJ2 encoding the inward-rectifier potassium channel have characteristics similar to mature cardiomyocytes including responsiveness to rate changes and potassium channel blockers. Our novel strategy could allow implementation of human induced pluripotent stem cell-derived cardiomyocytes in drug safety assessment for cardiac toxicity.