Genome-Wide Epigenetic and Transcriptomic Characterization of Human-Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Organoids.

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Ross, Alexander DB 
Forbester, Jessica L 

Human induced pluripotent stem cells (hiPSC) have been used to generate intestinal organoids that mimic key intestinal properties without the requirement for invasive procedures to obtain human tissues. The main protocols that have been described result in gut organoids that contain both intestinal epithelium as well as mesenchymal cells (2, 3). We have previously reported on human iPSC-derived intestinal organoids that can be propagated in long-term culture which contain solely epithelial cells (4–6). A pure epithelial model offers unique opportunities to study epithelial cell intrinsic and cell type specific mechanisms. Among these cellular processes are epigenetic mechanisms such as DNA methylation, which acts as a key regulator of intestinal epithelial development and regional identity (1, 7). The purpose of this study was to characterise iPSC-derived human intestinal epithelial organoids (iPSCo) by comparing these cultures with primary purified intestinal epithelial cells (IEC).

Epigenesis, Genetic, Epithelial Cells, Genome, Human, Humans, Induced Pluripotent Stem Cells, Intestinal Mucosa, Organoids, Transcriptome
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Cell Mol Gastroenterol Hepatol
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Elsevier BV
CICRA, Children with Crohn's and Colitis (unknown)
National Association for Colitis and Crohn's Disease (NACC) (M16-5)
Medical Research Council (MC_PC_12009)
National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/N001540/1)
European Research Council (741707)
European Commission Horizon 2020 (H2020) Societal Challenges (668294-2 INTENS)
JK was supported by Crohn’s & Colitis UK and Crohn’s in Childhood Research association (CICRA). GD and JF received core support from the Wellcome Trust. We would also like to thank the WTSI Core Scientific Operations team for conducting Illumina transcriptome sequencing. RNA-Sequencing was funded by the Wellcome Trust [206194]. LV is funded by the European Research Council advanced grant New-Chol (ERC: 741707), Cambridge University Hospitals NIHR Biomedical Research Center, core support from the Wellcome Trust and MRC to the Cambridge Stem Cell Institute (PSAG028) and the EU grant INTENS. AR is supported by the Wellcome Trust Interdisciplinary Programme in Translational Medicine and Therapeutics (TMAT) (100138/B/12/Z).