Nature20110512:Induction of functional hepatocyte-like cells from mouse fibrobla

shiyi

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. Induced hepatic differentiation has been achieved previously using embryonic stem cells or induced pluripotent stem cells. Particularly, hepatocytes generated from a patient’s own induced pluripotent stem cells could theoretically avoid immunological rejection. However, the induction of hepatocytes from induced 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, including neurons, cardiomyocytes and blood progenitors; however, it remains unclear whether these lineage-converted cells could repair damaged tissues in vivo. Here we demonstrate the direct induction of functional hepatocyte-like (iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4, Hnf1α and Foxa3, and inactivation of p19Arf. 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.

开心果王

实验室一直也想在直接重编程上做点东西，之前也瞄准了肝向分化。但是实验室刚刚起步，远不是他们的对手，看到这样的文章发表还是蛮激动的！不过我们还可以再进一步研究，比如效率、功能等，另外也可以向liver progenitor cells考虑，逆水行舟，不进则退！

shiyi

全文

shiyi

回复 开心果王 的帖子  O! J, `. z, K2 M# a: y
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加油加油！有志者事竟成！

shiyi

Supplementary Information 0 Z% b* E$ u; B2 r  }2 C

sannia

我现在还在苦攻iPSC和ESC向肝分化，有点担心是不是过时了啊。现在好像直接分化是王道啊。