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Chunk #0 — Globally similar ES cell and iPSC methylomes

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Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells.
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To assess the degree to which a somatic cell DNA methylome is reprogrammed into an ES-cell-like state by induction of a pluripotent state, we generated whole-genome, single-base resolution DNA methylomes of a range of human cell types using the shotgun bisulphite-sequencing method, MethylC-Seq18. Our central focus was a high-efficiency, feeder-free reprogramming system19, in which female adipose-derived stem cells (ADS) were reprogrammed into a pluripotent state by retroviral transformation with the OCT4, SOX2, KLF4 and MYC genes (ADS-iPSCs), satisfying the criteria for pluripotency in human cells20. Additionally, we analysed the DNA methylome of adipocytes derived from the ADS cells (ADS-adipose) through adipogenic differentiation conditions. Further, to explore the variation between independent iPSC lines potentially due to stochastic reprogramming events, progenitor somatic cell type, reprogramming technique and laboratory-specific effects, we generated full DNA methylomes for four additional iPSC lines that were isolated in an independent laboratory: an iPSC line generated by lentiviral integration of the OCT4, SOX2, NANOG and LIN28A genes into IMR90 lung fibroblasts (IMR90-iPSCs)5, and three iPSC lines generated by reprogramming of foreskin fibroblasts (FF) by non-integrating episomal vectors (FF-iPSC