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

Authors: Wei Tang1,2, Ren Guo2,3, Shi-jun Shen1, Yang Zheng2,3,4, Yu-ting Lu3,4,5, Meng-meng Jiang2,3,4, Xue Cui1,2, Ci-zhong Jiang1, Xin Xie1,2,5,6
1 Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-Based Biomedicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
2 CAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
3 University of Chinese Academy of Sciences, Beijing 100049, China
4 School of Life Science and Technology, ShanghaiTech University, Shanghai 201203, China
5 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
6 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
Correspondence to: Xin Xie: xxie@simm.ac.cn,
DOI: 10.1038/s41401-018-0170-z
Received: 9 July 2018
Accepted: 27 August 2018
Advance online: 12 October 2018

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, Hnf1α, or Hnf4α) 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.
Keywords: reprogramming; hepatic transdifferentiation; human urine-derived cells; chemical cocktail; regenerative medicine

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