DICP OpenIR
Subject Area物理化学
Direct Reprogramming of Human Fibroblasts to Functional and Expandable Hepatocytes
Huang, Pengyu1; Zhang, Ludi1; Gao, Yimeng1; He, Zhiying2; Yao, Dan3; Wu, Zhitao3; Cen, Jin1; Chen, Xiaotao1; Liu, Changcheng2; Hu, Yiping2; Lai, Dongmei4; Hu, Zhenlei5; Chen, Li6; Zhang, Ying6; Cheng, Xin1; Ma, Xiaojun6; Pan, Guoyu3; Wang, Xin7,8,9; Hui, Lijian1; LijianHui
Source PublicationCELL STEM CELL
2014-03-06
DOI10.1016/j.stem.2014.01.003
Volume14Issue:3Pages:370-384
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectCell & Tissue Engineering ; Cell Biology
WOS Research AreaCell Biology
WOS KeywordBIOARTIFICIAL LIVER ; DRUG-METABOLISM ; TRANSCRIPTION FACTORS ; P53-DEFICIENT MICE ; IN-VIVO ; CELLS ; CONVERSION ; CHALLENGES ; INDUCTION ; FAILURE
AbstractThe 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.
Language英语
WOS IDWOS:000332533400013
Citation statistics
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/144005
Collection中国科学院大连化学物理研究所
Corresponding AuthorLijianHui
Affiliation1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China
2.Second Mil Med Univ, Dept Cell Biol, Shanghai 200433, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Shanghai 201203, Peoples R China
4.Shanghai Jiao Tong Univ, Sch Med, Int Peace Matern & Child Hlth Hosp, Shanghai 200030, Peoples R China
5.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai 200127, Peoples R China
6.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Biomed Mat Engn, Dalian 116023, Peoples R China
7.Inner Mongolia Univ, Key Lab Natl Educ, Minist Mammalian Reprod Biol & Biotechnol, Hohhot 010021, Peoples R China
8.Univ Minnesota, Stem Cell Inst, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
9.Hepatoscience Inc, Palo Alto, CA 94303 USA
Recommended Citation
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.,...&LijianHui.(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.
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