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Chemical cocktails enable hepatic reprogramming of human urine-derived cells with a single transcription factor.

ABSTRACT: Human liver or hepatocyte transplantation is limited by a severe shortage of donor organs. Direct reprogramming of other adult cells into hepatic cells may offer a solution to this problem. In a previous study, we have generated hepatocyte-like cells from mouse fibroblasts using only one transcription factor (TF) plus a chemical cocktail. Here, we show that human urine-derived epithelial-like cells (hUCs) can also be transdifferentiated into human hepatocyte-like cells (hiHeps) using one TF (Foxa3, Hnf1?, or Hnf4?) plus the same chemical cocktail CRVPTD (C, CHIR99021; R, RepSox; V, VPA; P, Parnate; T, TTNPB; and D, Dznep). These hiHeps express multiple hepatocyte-specific genes and display functions characteristic of mature hepatocytes. With the introduction of the large T antigen, these hiHeps can be expanded in vitro and can restore liver function in mice with concanavalin-A-induced acute liver failure. Our study provides a strategy to generate functional hepatocyte-like cells from hUCs by using a single TF plus a chemical cocktail.

SUBMITTER: Tang W

PROVIDER: S-EPMC6786299 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor.

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Direct reprogramming of mouse fibroblasts into cardiomyocytes with chemical cocktails

2015-08-23 | GSE69924 | GEO

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Comprehensive screens and a universal zinc finger model enable transcription factor reprogramming 2 factor reprogrammingComprehensive screens and a universal zinc finger model enable transcription factor reprogramming

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Endoplasmic reticulum-derived bodies enable a single-cell chemical defense in Brassicaceae plants

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