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

	Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors
	Huang, PY; He, ZY; Ji, SY; Sun, HW; Xiang, D; Liu, CC; Hu, YP; Wang, X; Hui, LJ
刊名	NATURE
	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
内容类型	期刊论文
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
推荐引用方式 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.