Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver
Abstract
Hepatic oval cells are considered to be facultative hepatic stem cells(HSCs) that differentiate into hepatocytes and cholangiocytes in severely injured liver. Hepatic oval cells have also been implicated in tumorigenesis. However, their nature and origin remain elusive. To isolate and characterize mouse oval cells, we searched for cell surface molecules expressed on oval cells and analyzed their nature at the single-cell level by flow cytometric analysis and in the in vitro colony formation assay. We demonstrate that epithelial cell adhesion molecule (EpCAM) is expressed in both mouse normal cholangiocytes and oval cells, whereas its related protein, TROP2, is expressed exclusively in oval cells, establishing TROP2 as a novel marker to distinguish oval cells from normal cholangiocytes. EpCAM+ cells isolated from injured liver proliferate to form colonies in vitro, and the clonally expanded cells differentiate into hepatocytes and cholangiocytes,suggesting that the oval cell fraction contains potential HSCs. Interestingly,such cells with HSC characteristics exist among EpCAM+ cells of normal liver. Intriguingly, comparison of the colony formation of EpCAM+ cells in normal and injured liver reveals little difference in the number of potential HSCs, strongly suggesting that most proliferating mouse oval cells represent transit-amplifying cells rather than HSCs.
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Earlier FACS-based isolations of putative HPCs relied on a single selection marker or failed to fully exclude other non-parenchymal cell populations.
“Although previous studies have isolated putative HPCs using FACS isolation, these techniques are based on single selection markers37,8 or did not completely exclude other NPC populations37,52.”
From Hepatic progenitor cells of biliary origin with liver repopulation capacity (2015) · cites this paper as [8]
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Self-citation
- Authors
- Okabe, M., Tsukahara, Y., Tanaka, M., Suzuki, K., Saito, S., Kamiya, Y., Tsujimura, T., Nakamura, K., & Miyajima, A.
- Affiliations
- The University of Tokyo (JP)
- Hyogo Medical University (JP)
- LivTech, Miyamae-ku, Kawasaki, Kanagawa 216-0001, Japan.
- Corresponding author
- Tanaka, Minoru
- ORCID
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2009-06-01
- Volume
- 136
- Issue
- 11
- Pages
- 1951-1960
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2122114596
- Cited by
- 287
- References
- 76
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 6 · 2023: 9 · 2022: 15 · 2021: 11 · 2020: 13 · 2019: 20 · 2018: 20 · 2017: 24 · 2016: 24 · 2015: 26 · 2014: 26 · 2013: 27 · 2012: 19
- FWCI
- 12.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Development (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- hepatic stem cells, hepatic oval cells, EpCAM, TROP2, cholangiocytes, liver injury, hepatocyte differentiation, cholangiocyte differentiation, transit amplifying cells, cell surface markers, colony formation, mouse liver
- MeSH terms
- Epithelial Cell Adhesion Molecule, Animals, Antigens, Differentiation, Antigens, Neoplasm, Cell Differentiation, Cells, Cultured, Liver, Mice, Inbred C57BL, Proteins, Stem Cells, Cell Adhesion Molecules, Hepatocytes, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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