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Heterogeneous murine peribiliary glands orchestrate compartmentalized epithelial renewal.

Published version
Peer-reviewed

Repository DOI


Type

Article

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Authors

Singh, Serrena 
Lian, Qiuyu 
Budiman, Tifanny 
Taketo, Makoto M 
Simons, Benjamin D 

Abstract

The extrahepatic branches of the biliary tree have glands that connect to the surface epithelium through narrow pits. The duct epithelia undergo homeostatic renewal, yet the identity and multiplicity of cells that maintain this tissue is unknown. Using marker-free and targeted clonal fate mapping in mice, we provide evidence that the extrahepatic bile duct is compartmentalized. Pit cholangiocytes of extramural glands renewed the surface epithelium, whereas basally oriented cholangiocytes maintained the gland itself. In contrast, basally positioned cholangiocytes replenished the surface epithelium in mural glands. Single-cell sequencing identified genes enriched in the base and surface epithelial populations, with trajectory analysis showing graded gene expression between these compartments. Epithelia were plastic, changing cellular identity upon fasting and refeeding. Gain of canonical Wnt signaling caused basal cell expansion, gastric chief cell marker expression, and a decrease in surface epithelial markers. Our results identify the cellular hierarchy governing extrahepatic biliary epithelial renewal.

Description

Keywords

Lgr5, Muc6, Wnt, biliary glands, gastric, homeostasis, liver, stem cells, Animals, Mice, Biliary Tract, Bile Ducts, Extrahepatic, Epithelium, Epithelial Cells, Cell Proliferation

Journal Title

Dev Cell

Conference Name

Journal ISSN

1534-5807
1878-1551

Volume Title

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (219478/Z/19/Z)
Wellcome Trust (203151/Z/16/Z)
Medical Research Council (MC_PC_17230)
Wellcome Trust (203151/A/16/Z)