Direct Reprogramming of Human Fibroblasts to Functional and Expandable Hepatocytes

doi:10.1016/j.stem.2014.01.003

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	Direct Reprogramming of Human Fibroblasts to Functional and Expandable Hepatocytes
	Huang, Pengyu 3; Zhang, Ludi 3; Gao, Yimeng 3; He, Zhiying 4; Yao, Dan 2; Wu, Zhitao 2; Cen, Jin 3; Chen, Xiaotao 3; Liu, Changcheng 4; Hu, Yiping 4
刊名	CELL STEM CELL
	2014-03-06
卷号	14 期号:3 页码:370-384
ISSN号	1934-5909
DOI	10.1016/j.stem.2014.01.003
文献子类	Article
英文摘要	The generation of large numbers of functional human hepatocytes for cell-based approaches to liver disease is an important and unmet goal. Direct reprogramming of fibroblasts to hepatic lineages could offer a solution to this problem but so far has only been achieved with mouse cells. Here, we generated human induced hepatocytes (hiHeps) from fibroblasts by lentiviral expression of FOXA3, HNF1A, and HNF4A. hiHeps express hepatic gene programs, can be expanded in vitro, and display functions characteristic of mature hepatocytes, including cytochrome P450 enzyme activity and biliary drug clearance. Upon transplantation into mice with concanavalin-A-induced acute liver failure and fatal metabolic liver disease due to fumarylacetoacetate dehydrolase (Fah) deficiency, hiHeps restore the liver function and prolong survival. Collectively, our results demonstrate successful lineage conversion of nonhepatic human cells into mature hepatocytes with potential for biomedical and pharmaceutical applications.
资助项目	Chinese Academy of Sciences (CAS)[XDA01030301] ; Chinese Academy of Sciences (CAS)[XDA01020308] ; Ministry of Science and Technology (MOST) of China[2012CB945001] ; National Science Foundation of China (NSFC)[913193023] ; National Science Foundation of China (NSFC)[31225016] ; MOST of China[2011CB966200] ; NSFC[31271469] ; NSFC[31271474] ; NSFC[31271042] ; NSFC[81302836] ; NSFC[21076207] ; NSFC[81101757] ; MOST[2012ZX09301001-006] ; MOST[2012ZX09302003] ; CAS (the Hundred Talents Program)[00000000] ; CAS[XDA01030303]
WOS关键词	BIOARTIFICIAL LIVER ; DRUG-METABOLISM ; TRANSCRIPTION FACTORS ; P53-DEFICIENT MICE ; IN-VIVO ; CELLS ; CONVERSION ; CHALLENGES ; INDUCTION ; FAILURE
WOS研究方向	Cell Biology
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000332533400013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277158]
专题	药物安全性评价中心
通讯作者	Hui, Lijian
作者单位	1.Hepatoscience Inc, Palo Alto, CA 94303 USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai 201203, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China; 4.Second Mil Med Univ, Dept Cell Biol, Shanghai 200433, Peoples R China; 5.Shanghai Jiao Tong Univ, Sch Med, Int Peace Matern & Child Hlth Hosp, Shanghai 200030, Peoples R China; 6.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai 200127, Peoples R China; 7.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Biomed Mat Engn, Dalian 116023, Peoples R China; 8.Inner Mongolia Univ, Key Lab Natl Educ, Minist Mammalian Reprod Biol & Biotechnol, Hohhot 010021, Peoples R China; 9.Univ Minnesota, Stem Cell Inst, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA;
推荐引用方式 GB/T 7714	Huang, Pengyu,Zhang, Ludi,Gao, Yimeng,et al. Direct Reprogramming of Human Fibroblasts to Functional and Expandable Hepatocytes[J]. CELL STEM CELL,2014,14(3):370-384.
APA	Huang, Pengyu.,Zhang, Ludi.,Gao, Yimeng.,He, Zhiying.,Yao, Dan.,...&Hui, Lijian.(2014).Direct Reprogramming of Human Fibroblasts to Functional and Expandable Hepatocytes.CELL STEM CELL,14(3),370-384.
MLA	Huang, Pengyu,et al."Direct Reprogramming of Human Fibroblasts to Functional and Expandable Hepatocytes".CELL STEM CELL 14.3(2014):370-384.