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Chemical cocktails enable hepatic reprogramming of human urine-derived cells with a single transcription factor
2019-05
发表期刊ACTA PHARMACOLOGICA SINICA (IF:6.9[JCR-2023],7.6[5-Year])
ISSN1671-4083
卷号40期号:5页码:620-629
发表状态已发表
DOI10.1038/s41401-018-0170-z
摘要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 alpha, or Hnf4 alpha) 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.
关键词reprogramming hepatic transdifferentiation human urine-derived cells chemical cocktail regenerative medicine
收录类别SCI ; SCIE ; CSCD
语种英语
资助项目National Natural Science Foundation of China[81425024] ; National Natural Science Foundation of China[31371511] ; National Natural Science Foundation of China[81472862] ; National Natural Science Foundation of China[31501189]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
WOS类目Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号WOS:000466149400006
出版者NATURE PUBLISHING GROUP
WOS关键词ACUTE LIVER-FAILURE ; PLURIPOTENT STEM-CELLS ; HEPATOCYTE-LIKE CELLS ; MOUSE FIBROBLASTS ; GENE-EXPRESSION ; TRANSPLANTATION ; GENERATION ; MAINTENANCE ; METABOLISM ; DISEASE
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/40830
专题生命科学与技术学院_硕士生
生命科学与技术学院_博士生
通讯作者Xie, Xin
作者单位
1.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Sch Life Sci & Technol, Lab Receptor Based Biomed, Shanghai 200092, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201203, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China
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Tang, Wei,Guo, Ren,Shen, Shi-jun,et al. Chemical cocktails enable hepatic reprogramming of human urine-derived cells with a single transcription factor[J]. ACTA PHARMACOLOGICA SINICA,2019,40(5):620-629.
APA Tang, Wei.,Guo, Ren.,Shen, Shi-jun.,Zheng, Yang.,Lu, Yu-ting.,...&Xie, Xin.(2019).Chemical cocktails enable hepatic reprogramming of human urine-derived cells with a single transcription factor.ACTA PHARMACOLOGICA SINICA,40(5),620-629.
MLA Tang, Wei,et al."Chemical cocktails enable hepatic reprogramming of human urine-derived cells with a single transcription factor".ACTA PHARMACOLOGICA SINICA 40.5(2019):620-629.
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