Induction of functional hepatocyte-like cells from mouse.pdfVIP

LETTER doi:10.1038/nature10116 Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors 1 1,2 1 1 2 1,2 2 1,3,4 1 Pengyu Huang , Zhiying He , Shuyi Ji , Huawang Sun , Dao Xiang , Changcheng Liu , Yiping Hu , Xin Wang Lijian Hui The generation of functional hepatocytes independent of donor liver (PAS) staining (Fig. 1d) and uptake of DiI-labelled acetylated low- organs is of great therapeutic interest with regard to regenerative density lipoprotein (DiI-ac-LDL, Fig. 1e). These results indicated that medicine and possible cures for liver disease1. Induced hepatic dif- p19 Arf 2/2 TTFs were converted into cells with significant hepatic gene ferentiation has been achieved previously using embryonic stem expression and hepatic functions. cells or induced pluripotent stem cells2–8. Particularly, hepatocytes Next, we determined the key factors required for hepatic conver- generated from a patient’s own induced pluripotent stem cells could sion. On the basis of previous reports16–19, we established combinations theoretically avoid immunological rejection. However, the induc- of six factors (6TF), including Foxa2, Foxa3, Hnf1a, Hnf4a, Hnf6 and tion of hepatocytes from induced pluripotent stem cells is a compli- Gata4, and eight factors (8TF), including 6TF plus Foxa1 and Hlf. cated process that would probably be replaced with the arrival of Either 6TF or 8TF converted TTFs to epithelial colonies with hepatic improved technology. Overexpression of lineage-specific transcr