Heterogeneity and Stochastic Growth Regulation of Biliary Epithelial Cells Dictate Dynamic Epithelial Tissue Remodeling

Overview

Journal Elife

Specialty Biology

Date 2016 Jul 20

PMID 27431614

Citations 51

Authors

Kenji Kamimoto

Kota Kaneko

Cindy Yuet-Yin Kok

Hajime Okada

Atsushi Miyajima

Tohru Itoh

Affiliations

Soon will be listed here.

Abstract

Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity.

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