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Semin Liver Dis 2020; 40(04): 365-372
DOI: 10.1055/s-0040-1709679
Review Article

Hepatobiliary Differentiation: Principles from Embryonic Liver Development

Scott H. Freeburg
1   Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Wolfram Goessling
1   Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
2   Broad Institute of MIT and Harvard, Cambridge, Massachusetts
3   Harvard Stem Cell Institute, Cambridge, Massachusetts
4   Dana-Farber Cancer Institute, Boston, Massachusetts
5   Harvard-MIT Division of Health Science and Technology, Cambridge, Massachusetts
6   Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts
› Author Affiliations Acknowledgments This study was funded by NIH R24OD017870, R01DK090311, and R01DK105198 to W.G.
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Abstract

Hepatocytes and biliary epithelial cells (BECs), the two endodermal cell types of the liver, originate from progenitor cells called hepatoblasts. Based principally on in vitro data, hepatoblasts are thought to be bipotent stem cells with the potential to produce both hepatocytes and BECs. However, robust in vivo evidence for this model has only recently emerged. We examine the molecular mechanisms that stimulate hepatoblast differentiation into hepatocytes or BECs. In the absence of extrinsic cues, the default fate of hepatoblasts is hepatocyte differentiation. Inductive cues from the hepatic portal vein, however, initiate transcription factor expression in hepatoblasts, driving biliary specification. Defining the mechanisms of hepatobiliary differentiation provides important insights into congenital disorders, such as Alagille syndrome, and may help to better characterize the poorly understood hepatic lineage relationships observed during regeneration from liver injury.

Keywords

liver development - organogenesis - cell differentiation


Publication History

Article published online:
11 June 2020

© 2020. Thieme. All rights reserved.

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