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Publication : Heterogeneous murine peribiliary glands orchestrate compartmentalized epithelial renewal.

First Author  Singh S Year  2023
Journal  Dev Cell Volume  58
Issue  23 Pages  2732-2745.e5
PubMed ID  37909044 Mgi Jnum  J:342981
Mgi Id  MGI:7561420 Doi  10.1016/j.devcel.2023.10.004
Citation  Singh S, et al. (2023) Heterogeneous murine peribiliary glands orchestrate compartmentalized epithelial renewal. Dev Cell
abstractText  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.
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