Isolation of Bipotential Liver Progenitor Cells from Neonatal Mouse Liver
Liver stem/progenitor cells (LPCs) are defined as bipotential cells differentiating into both hepatocytes and cholangiocytes. The Notch, TGFβ, and Hippo pathways have been implicated in lineage determination of LPCs during development and regeneration. However, the molecular mechanisms governing the lineage specification have not been fully elucidated, yet. Epithelial adhesion molecule (EpCAM) is a marker of cholangiocytes and of LPCs. We found that EpCAM+ cells isolated from neonatal liver contain LPCs that clonally proliferate and are bipotential in vitro and in vivo. Furthermore, EpCAM+ progenies keep the capacity of bidirectional differentiation even after long-term culture. These cells are useful to investigate the molecular mechanisms regulating lineage commitment and epithelial differentiation of LPCs.
Key wordsTissue stem cell Liver Neonate Bipotential Hepatocyte Cholangiocyte Liver stem/progenitor cell Fluorescence-activated cell sorting Colony assay Clonal culture
I thank Dr. Toshihiro Mitaka and Dr. Norihisa Ichinohe for helpful discussion and Ms. Yumiko Tsukamoto and Ms. Minako Kuwano for technical assistance. This work is supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan, Grants-in-Aid for Scientific Research (C) (25460271, 16 K08716), and Grants-in-Aid for Scientific Research on Innovative Areas “Stem Cell Aging and Disease” (17H05653).
- 6.Kamimoto K, Kaneko K, Kok CY et al (2016) Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling. Elife 5:e15034Google Scholar