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Stem Cell Reports. 2017 Aug 8;9(2):478-489. doi: 10.1016/j.stemcr.2017.06.003. Epub 2017 Jul 6.

Adult Mouse Liver Contains Two Distinct Populations of Cholangiocytes.

Author information

1
Oregon Stem Cell Center, Oregon Health and Science University, Portland, OR 97239, USA.
2
Papé Family Pediatric Research Institute, Oregon Health and Science University, Portland, OR 97239, USA.
3
Department of Pathology, Texas Children's Hospital, Houston, TX 77030, USA.
4
Oregon Stem Cell Center, Oregon Health and Science University, Portland, OR 97239, USA; Papé Family Pediatric Research Institute, Oregon Health and Science University, Portland, OR 97239, USA; Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239, USA. Electronic address: grompem@ohsu.edu.

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

PMID:
28689996
PMCID:
PMC5549808
DOI:
10.1016/j.stemcr.2017.06.003
[Indexed for MEDLINE]
Free PMC Article

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