E-GEOD-48486 - Reprogramming fibroblasts into bi-potential hepatic stem cells by defined factors
Released on 19 July 2013, last updated on 3 June 2014
Recent studies have demonstrated direct reprogramming of fibroblasts into a range of somatic cell types, but to date stem/progenitor cells have only been reprogrammed for the blood and neuronal lineages. We previously reported generation of induced hepatocyte-like (iHep) cells by transduction of Gata4, Hnf1α, and Foxa3 in p19 Arf null mouse embryonic fibroblasts (MEFs). Here, we show that Hnf1β and Foxa3, liver organogenesis transcription factors, are sufficient to reprogram MEFs into induced hepatic stem cells (iHepSCs). iHepSCs can be stably expanded in vitro and possess the potential of bi-directional differentiation into both hepatocytic and cholangiocytic lineages. In the injured liver of fumarylacetoacetate hydrolase (Fah)-deficient mice, repopulating iHepSCs become hepatocyte-like cells. They also engraft as cholangiocytes into bile ducts of mice with DDC-induced bile ductular injury. Lineage-conversion into bi-potential expandable iHepSCs provides a strategy to enable efficient derivation of both hepatocytes and cholangiocytes for use in disease modeling and tissue engineering. iHepSCs were converted form fibroblasts by transduction of Hnf1β and Foxa3. iHepSCs were induced to differentiate into hepatocyte-like cells and cholangiocytes in vitro. Totally, 9 samples including four clones of iHepSCS, one clone of LEPCs, two samples of MEFs and two samples of iHepSCs-derived cholangocytes were analyzed.
transcription profiling by array
Pu You <firstname.lastname@example.org>, Bing Yu, Chang-Cheng Liu, Chun-Sheng Han, Dao Xiang, Fei Chen, Hai-Ying Zhu, Jian-Xiu Li, Kirk J Wangensteen, Li-Jian Hui, Min-Jun Wang, Qing-Wang Han, Uyunbilig Borjigin, Wen-Lin Li, Xi-Wen Lin, Xiao-Yuan Zi, Xin Wang, Yi-Ping Hu, Yufang Shi, Zhi-Ying He
Reprogramming Fibroblasts into Bipotential Hepatic Stem Cells by Defined Factors. Yu B, He ZY, You P, Han QW, Xiang D, Chen F, Wang MJ, Liu CC, Lin XW, Borjigin U, Zi XY, Li JX, Zhu HY, Li WL, Han CS, Wangensteen KJ, Shi Y, Hui LJ, Wang X, Hu YP. , Europe PMC 23871605