Direct conversion of mouse fibroblasts into cholangiocyte progenitor cells

We describe that Hnf1a and Foxa3 dramatically facilitate the robust generation of iHepSCs. Notably, the prolonged in vitro culture of Hnf1a and Foxa3 derived iHepSCs induce Notch signaling-mediated secondary conversion into cholangiocyte progenitor-like cells displaying the dramatically enhanced differentiation capacity into the mature cholangiocytes in vitro and in vivo. Our study provides the novel two-step approach for obtaining cholangiocyte progenitor-like cells using defined factors. Overall design: Comparative analyses between induced hepatic stem-like cells (iHepSCs) generated from fibroblasts using two different combinations, 1a3 (Foxa3/Hnf1a) and 1b3 (Foxa3/Hnf1b; Yu et al. Cell Stem Cell 2013)