Mouse hepatoblasts at distinct developmental stages are characterized by expression of EpCAM and DLK1: drastic change of EpCAM expression during liver development
Open accessAbstract
Hepatoblasts are hepatic progenitor cells that expand and give rise to either hepatocyte or cholangiocytes during liver development. We previously reported that delta-like 1 homolog (DLK1) is expressed in the mouse liver primordium at embryonic day (E) 10.5 and that DLK1(+) cells in E14.5 liver contain high proliferative and bipotential hepatoblasts. While the expression of epithelial cell adhesion molecule (EpCAM) in hepatic stem/progenitor cells has been reported, its expression profile at an early stage of liver development remains unknown. In this study, we show that EpCAM is expressed in mouse liver bud at E9.5 and that EpCAM(+)DLK1(+) hepatoblasts form hepatic cords at the early stage of hepatogenesis. DLK1(+) cells of E11.5 liver were fractionated into EpCAM(+) and EpCAM(-) cells; one forth of EpCAM(+)DLK1(+) cells formed a colony in vitro whereas EpCAM(-)DLK1(+) cells rarely did it. Moreover, EpCAM(+)DLK1(+) cells contained cells capable of forming a large colony, indicating that EpCAM(+)DLK1(+) cells in E11.5 liver contain early hepatoblasts with high proliferation potential. Interestingly, EpCAM expression in hepatoblasts was dramatically reduced along with liver development and the colony-forming capacities of both EpCAM(+)DLK1(+) and EpCAM(-)DLK1(+) cells were comparable in E14.5 liver. It strongly suggested that most of mouse hepatoblasts are losing EpCAM expression at this stage. Moreover, we provide evidence that EpCAM(+)DLK1(+) cells in E11.5 liver contain extrahepatic bile duct cells as well as hepatoblasts, while EpCAM(-)DLK1(+) cells contain mesothelial cell precursors. Thus, the expression of EpCAM and DLK1 suggests the developmental pathways of mouse liver progenitors.
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The organization of the sinusoidal capillaries abuts HSECs against hepatic and mesenchymal lineages, which robustly express the Notch inhibitor Dlk1.
“In addition, the organization of the sinusoidal capillaries abuts HSECs against hepatic and mesenchymal lineages, which robustly express the Notch inhibitor Dlk1”
From Single-Cell Transcriptomics Reveals Early Emergence of Liver Parenchymal and Non-parenchymal Cell Lineages (2020) · cites this paper as Tanaka et al., 2009
Section 2.6 reports high DLK1 expression in mouse hepatoblasts, but describes the mesothelial-cell-containing population as DLK1-low; it does not establish robust expression across hepatic and mesenchymal lineages. The cited passages do not describe sinusoidal capillaries placing HSECs next to those cells or identify DLK1 as a Notch inhibitor. Page numbers are unavailable in our copy. (LLM, conf=0.85)
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- Authors
- Tanaka, M., Okabe, M., Suzuki, K., Kamiya, Y., Tsukahara, Y., Saito, S., & Miyajima, A.
- Affiliations
- Japan Science and Technology Agency (JP)
- The University of Tokyo (JP)
- Corresponding author
- Tanaka, Minoru
- Venue
- Mechanisms of Development
- Publisher
- Elsevier BV
- Published
- 2009-08
- Volume
- 126
- Issue
- 8-9
- Pages
- 665-676
- ISSN
- 0925-4773 (ISSN-L)
- OpenAlex
- W2068185076
- Cited by
- 124
- References
- 42
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 11 · 2019: 12 · 2018: 12 · 2017: 12 · 2016: 9 · 2015: 13 · 2014: 9 · 2013: 7 · 2012: 8
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1482 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Mechanisms of Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Science and Technology Agency
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- hepatoblasts, EpCAM, DLK1, liver development, hepatogenesis, hepatic progenitor cells, colony-forming capacity, bile duct cells, mouse embryo
- MeSH terms
- Epithelial Cell Adhesion Molecule, Animals, Antigens, Neoplasm, Bile Ducts, Calcium-Binding Proteins, Flow Cytometry, Immunohistochemistry, Liver, Mice, Inbred C57BL, Models, Biological, Time Factors, Cell Adhesion Molecules, Gene Expression Regulation, Developmental, Gene Expression Profiling, Hepatocytes, Intercellular Signaling Peptides and Proteins, Mice
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