Human iPSC Derived Posterior Gut Progenitors Are Expandable and Capable of Forming Gut and Liver Organoids
Date: 8 Feb 2018
Early endoderm progenitors naturally possess robust propagating potential to develop majority of meter-long gastrointestinal tracts and are therefore considered as a promising source for therapy. Here, we demonstrated the reproducible generation of human CDX2+ posterior gut endoderm cells (PGECs) from five induced pluripotent stem cell clones by manipulating FGF, TGF and Wnt signaling. Transcriptome analysis suggested that putative PGECs harbored an intermediate signature profile between definitive endoderm and organ-specific endoderm. We found combinatorial EGF, VEGF, FGF2, Chir99021 and A83-01 treatments selectively amplify storable PGECs up to 1021 cell-scale without any gene transduction or feeder use. PGECs, compared with iPSCs, showed stable differentiation propensity into multiple endodermal lineages without teratoma formation. Furthermore, transplantation of PGECs derived liver bud organoids showed therapeutic potential against fulminant liver failure. Together, the robustly amplified PGECs may be a promising cellular source of endoderm-derived organoids for studying human development, modeling disease and ultimately therapy.
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