Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Miyajima A, Tanaka M, Itoh T (2014) Stem Progenitor cell sin liver development, homeostasis, regeneration, and reprogramming. Cell Stem Cell 14:261–274
Espanol-Suner R, Carpentier R, Van HN et al (2012) Liver progenitor cells yield functional hepatocytes in response to chronic liver injury in mice. Gastroenterology 143:1564–1575 e1567
Malato Y, Naqvi S, Schurmann N et al (2011) Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration. J Clin Invest 121:4850–4860
Choi TY, Ninov N, Stainer DY et al (2014) Extensive conversion of hepatic biliary epithelial cells to hepatocytes after near total loss of hepatocytes in zebrafish. Gastroenterology 146:776–788
Raven A, Lu WY, Man TY et al (2017) Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration. Nature 547:350–354
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:e15034
Li B, DorrellC CPS et al (2017) Adult mouse liver contains two distinct populations of cholangiocytes. Stem Cell Reports 9:478–489
Tanimizu N, Kobayashi S, Ichinohe N et al (2014) Downregulation of miR122 by grainyhead-like 2 restricts the hepatocytic differentiation potential of adult liver progenitor cells. Development 141:4448–4456
Acknowledgments
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).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Tanimizu, N. (2019). Isolation of Bipotential Liver Progenitor Cells from Neonatal Mouse Liver. In: Tanimizu, N. (eds) Hepatic Stem Cells . Methods in Molecular Biology, vol 1905. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8961-4_2
Download citation
DOI: https://doi.org/10.1007/978-1-4939-8961-4_2
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-8960-7
Online ISBN: 978-1-4939-8961-4
eBook Packages: Springer Protocols