Direct Conversion of Mouse Fibroblasts into Cholangiocyte Progenitor Cells

Publication date: Available online 29 March 2018 Source:Stem Cell Reports Author(s): Kyung Tae Lim, Jonghun Kim, Seon In Hwang, Ludi Zhang, Heonjong Han, Dasom Bae, Kee-Pyo Kim, Yi-Ping Hu, Hans R. Schöler, Insuk Lee, Lijian Hui, Dong Wook Han Disorders of the biliary epithelium, known as cholangiopathies, cause severe and irreversible liver diseases. The limited accessibility of bile duct precludes modeling of several cholangiocyte-mediated diseases. Therefore, novel approaches for obtaining functional cholangiocytes with high purity are needed. Previous work has shown that the combination of Hnf1β and Foxa3 could directly convert mouse fibroblasts into bipotential hepatic stem cell-like cells, termed iHepSCs. However, the efficiency of converting fibroblasts into iHepSCs is low, and these iHepSCs exhibit extremely low differentiation potential into cholangiocytes, thus hindering the translation of iHepSCs to the clinic. Here, we describe that the expression of Hnf1α and Foxa3 dramatically facilitates the robust generation of iHepSCs. Notably, prolonged in vitro culture of Hnf1α- and Foxa3-derived iHepSCs induces a Notch signaling-mediated secondary conversion into cholangiocyte progenitor-like cells that display dramatically enhanced differentiation capacity into mature cholangiocytes. Our study provides a robust two-step approach for obtaining cholangiocyte progenitor-like cells using defined factors. Graphical abstract Teaser In this article, Han and co...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research