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Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors

文献类型:期刊论文

作者Huang, PY; He, ZY; Ji, SY; Sun, HW; Xiang, D; Liu, CC; Hu, YP; Wang, X; Hui, LJ
刊名NATURE
出版日期2011
卷号475期号:7356页码:386-U142
通讯作者Hui, LJ (reprint author), Chinese Acad Sci, Lab Mol Cell Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Yueyang Rd 320, Shanghai 200031, Peoples R China.,ljhui@sibs.ac.cn
英文摘要The generation of functional hepatocytes independent of donor liver organs is of great therapeutic interest with regard to regenerative medicine and possible cures for liver disease(1). Induced hepatic differentiation has been achieved previously using embryonic stem cells or induced pluripotent stem cells(2-8). Particularly, hepatocytes generated froma patient's own induced pluripotent stem cells could theoretically avoid immunological rejection. However, the induction of hepatocytes frominduced pluripotent stem cells is a complicated process that would probably be replaced with the arrival of improved technology. Overexpression of lineage-specific transcription factors directly converts terminally differentiated cells into some other lineages(9-12), including neurons(13), cardiomyocytes(14) and blood progenitors(15); however, it remains unclear whether these lineage-converted cells could repair damaged tissues in vivo. Here we demonstrate the direct induction of functional hepatocytelike (iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4, Hnf1 alpha and Foxa3, and inactivation of p19(Arf). iHep cells show typical epithelial morphology, express hepatic genes and acquire hepatocyte functions. Notably, transplanted iHep cells repopulate the livers of fumarylacetoacetate-hydrolase-deficient (Fah(-/-)) mice and rescue almost half of recipients from death by restoring liver functions. Our study provides a novel strategy to generate functional hepatocyte-like cells for the purpose of liver engineering and regenerative medicine.
学科主题Science & Technology - Other Topics
类目[WOS]Multidisciplinary Sciences
关键词[WOS]ENRICHED TRANSCRIPTION FACTORS ; EMBRYONIC STEM-CELLS ; TYROSINEMIA TYPE-I ; PANCREAS PROGENITORS ; HEPATIC-DYSFUNCTION ; DIRECT CONVERSION ; GENE-EXPRESSION ; FACTOR NETWORK ; LIVER-FUNCTION ; MURINE MODEL
收录类别SCI
语种英语
WOS记录号WOS:000292911200044
版本出版稿
源URL[http://202.127.25.143/handle/331003/895]  
专题上海生化细胞研究所_上海生科院生化细胞研究所
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GB/T 7714
Huang, PY,He, ZY,Ji, SY,et al. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors[J]. NATURE,2011,475(7356):386-U142.
APA Huang, PY.,He, ZY.,Ji, SY.,Sun, HW.,Xiang, D.,...&Hui, LJ.(2011).Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors.NATURE,475(7356),386-U142.
MLA Huang, PY,et al."Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors".NATURE 475.7356(2011):386-U142.

入库方式: OAI收割

来源:上海生物化学与细胞生物学研究所

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