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Direct Conversion of Mouse Fibroblasts into Cholangiocyte Progenitor Cells

Published version
Peer-reviewed

Type

Article

Change log

Authors

Lim, KT 
Kim, Jonghun 
Hwnag, Seon In 
Zhang, Ludi 
Han, Heonjong 

Abstract

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.

Description

Keywords

direct conversion, cholangiocyte progenitor cells, hepatic stem cells, Notch signal

Journal Title

Stem Cell Reports

Conference Name

Journal ISSN

2213-6711
2213-6711

Volume Title

10

Publisher

Elsevier