Adult Mouse Liver Contains Two Distinct Populations of Cholangiocytes

Bin Li; Craig Dorrell; Pamela S. Canaday; Carl Pelz; Annelise Haft; Milton Finegold; Markus Grompe

doi:10.1016/j.stemcr.2017.06.003

Adult Mouse Liver Contains Two Distinct Populations of Cholangiocytes

Bin Li
, Craig Dorrell
, Pamela S. Canaday
, Carl Pelz
, Annelise Haft
, Milton Finegold
, Markus Grompe

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

The biliary system plays an important role in several acquired and genetic disorders of the liver. We have previously shown that biliary duct epithelium contains cells giving rise to proliferative Lgr5⁺ organoids in vitro. However, it remained unknown whether all biliary cells or only a specific subset had this clonogenic activity. The cell surface protease ST14 was identified as a positive marker for the clonogenic subset of cholangiocytes and was used to separate clonogenic and non-clonogenic duct cells by fluorescence-activated cell sorting. Only ST14^hi duct cells had the ability to generate organoids that could be serially passaged. The gene expression profiles of clonogenic and non-clonogenic duct cells were similar, but several hundred genes were differentially expressed. RNA fluorescence in situ hybridization showed that clonogenic duct cells are interspersed among regular biliary epithelium at a ∼1:3 ratio. We conclude that adult murine cholangiocytes can be subdivided into two populations differing in their proliferative capacity.

Original language	English (US)
Pages (from-to)	478-489
Number of pages	12
Journal	Stem Cell Reports
Volume	9
Issue number	2
DOIs	https://doi.org/10.1016/j.stemcr.2017.06.003
State	Published - Aug 8 2017

Funding

This work was supported by NIH grants R01-DK051592 and R01 DK083355 to M.G. The authors thank OHSU core services Massively Parallel Sequencing Shared Resource, OHSU Flow Cytometry Shared Resources, Histopathology Shared Resources, and Advanced Light Microscopy core. We thank Milton Finegold and Angela Major for histology assistance. We also thank Leslie Wakefield, Devorah Goldman, Qingshuo Zhang, Yuhan Wang, and Branden Tarlow for their excellent technical assistance. M.G. is a founder and shareholder of Yecuris. OHSU has commercially licensed MIC1-1C3; authors C.D. and M.G. are inventors of this antibody. This potential conflict of interest has been reviewed and managed by OHSU.

Funders	Funder number
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	R01 DK083355
National Institute of Diabetes and Digestive and Kidney Diseases	R01DK051592
Oregon State University/Oregon Health and Science University

Keywords

bile duct
biliary tree
cholangiocyte
clonogenic assay
liver
liver regeneration
organoid
progenitor

ASJC Scopus subject areas

Biochemistry
Genetics
Developmental Biology
Cell Biology

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10.1016/j.stemcr.2017.06.003

Cite this

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title = "Adult Mouse Liver Contains Two Distinct Populations of Cholangiocytes",

abstract = "The biliary system plays an important role in several acquired and genetic disorders of the liver. We have previously shown that biliary duct epithelium contains cells giving rise to proliferative Lgr5+ organoids in vitro. However, it remained unknown whether all biliary cells or only a specific subset had this clonogenic activity. The cell surface protease ST14 was identified as a positive marker for the clonogenic subset of cholangiocytes and was used to separate clonogenic and non-clonogenic duct cells by fluorescence-activated cell sorting. Only ST14hi duct cells had the ability to generate organoids that could be serially passaged. The gene expression profiles of clonogenic and non-clonogenic duct cells were similar, but several hundred genes were differentially expressed. RNA fluorescence in situ hybridization showed that clonogenic duct cells are interspersed among regular biliary epithelium at a ∼1:3 ratio. We conclude that adult murine cholangiocytes can be subdivided into two populations differing in their proliferative capacity.",

keywords = "bile duct, biliary tree, cholangiocyte, clonogenic assay, liver, liver regeneration, organoid, progenitor",

author = "Bin Li and Craig Dorrell and Canaday, \{Pamela S.\} and Carl Pelz and Annelise Haft and Milton Finegold and Markus Grompe",

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AU - Li, Bin

AU - Dorrell, Craig

AU - Canaday, Pamela S.

AU - Pelz, Carl

AU - Haft, Annelise

AU - Finegold, Milton

AU - Grompe, Markus

PY - 2017/8/8

Y1 - 2017/8/8

N2 - The biliary system plays an important role in several acquired and genetic disorders of the liver. We have previously shown that biliary duct epithelium contains cells giving rise to proliferative Lgr5+ organoids in vitro. However, it remained unknown whether all biliary cells or only a specific subset had this clonogenic activity. The cell surface protease ST14 was identified as a positive marker for the clonogenic subset of cholangiocytes and was used to separate clonogenic and non-clonogenic duct cells by fluorescence-activated cell sorting. Only ST14hi duct cells had the ability to generate organoids that could be serially passaged. The gene expression profiles of clonogenic and non-clonogenic duct cells were similar, but several hundred genes were differentially expressed. RNA fluorescence in situ hybridization showed that clonogenic duct cells are interspersed among regular biliary epithelium at a ∼1:3 ratio. We conclude that adult murine cholangiocytes can be subdivided into two populations differing in their proliferative capacity.

AB - The biliary system plays an important role in several acquired and genetic disorders of the liver. We have previously shown that biliary duct epithelium contains cells giving rise to proliferative Lgr5+ organoids in vitro. However, it remained unknown whether all biliary cells or only a specific subset had this clonogenic activity. The cell surface protease ST14 was identified as a positive marker for the clonogenic subset of cholangiocytes and was used to separate clonogenic and non-clonogenic duct cells by fluorescence-activated cell sorting. Only ST14hi duct cells had the ability to generate organoids that could be serially passaged. The gene expression profiles of clonogenic and non-clonogenic duct cells were similar, but several hundred genes were differentially expressed. RNA fluorescence in situ hybridization showed that clonogenic duct cells are interspersed among regular biliary epithelium at a ∼1:3 ratio. We conclude that adult murine cholangiocytes can be subdivided into two populations differing in their proliferative capacity.

KW - bile duct

KW - biliary tree

KW - cholangiocyte

KW - clonogenic assay

KW - liver

KW - liver regeneration

KW - organoid

KW - progenitor

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Adult Mouse Liver Contains Two Distinct Populations of Cholangiocytes

Abstract

Funding

Keywords

ASJC Scopus subject areas

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