PUBLICATION

Contributions of biliary epithelial cells to hepatocyte homeostasis and regeneration in zebrafish

Authors
Zhang, W., Chen, J., Ni, R., Yang, Q., Luo, L., He, J.
ID
ZDB-PUB-210306-2
Date
2021
Source
iScience   24: 102142 (Journal)
Registered Authors
He, Jianbo, Luo, Lingfei
Keywords
cellular biology, cellular physiology, developmental biology
MeSH Terms
none
PubMed
33665561 Full text @ iScience
Abstract
Whether transdifferentiation of the biliary epithelial cells (BECs) to hepatocytes occurs under physiological conditions and contributes to liver homeostasis remains under long-term debate. Similar questions have been raised under pathological circumstances if a fibrotic liver is suffered from severe injuries. To address these questions in zebrafish, we established a sensitive lineage tracing system specific for the detection of BEC-derived hepatocytes. The BEC-to-hepatocyte transdifferentiation occurred and became minor contributors to hepatocyte homeostasis in a portion of adult individuals. The BEC-derived hepatocytes distributed in clusters in the liver. When a fibrotic liver underwent extreme hepatocyte damages, BEC-to-hepatocyte transdifferentiation acted as the major origin of regenerating hepatocytes. In contrast, partial hepatectomy failed to induce the BEC-to-hepatocyte conversion. In conclusion, based on a sensitive lineage tracing system, our results suggest that BECs are able to transdifferentiate into hepatocytes and contribute to both physiological hepatocyte homeostasis and pathological regeneration.
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cq1TgTransgenic Insertion
    cq4TgTransgenic Insertion
      cq74TgTransgenic Insertion
        cq129TgTransgenic Insertion
          cq130TgTransgenic Insertion
            s928TgTransgenic Insertion
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              Antibodies
              Name Type Antigen Genes Isotypes Host Organism
              Ab2-col1polyclonal
                		IgGRabbit
                Ab-2F11monoclonalIgG1Mouse
                zn-5monoclonalIgG1Mouse
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                Engineered Foreign Genes
                Marker Marker Type Name
                CreEFGCre
                Dendra2EFGDendra2
                DsRedEFGDsRed
                DsRed2EFGDsRed2
                EGFPEFGEGFP
                NTREFGNTR
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                Citation
                Zhang, W., Chen, J., Ni, R., Yang, Q., Luo, L., He, J. (2021) Contributions of biliary epithelial cells to hepatocyte homeostasis and regeneration in zebrafish. iScience. 24:102142.