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Genetic Lineage Tracing of Biliary Epithelial Cells

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Hepatic Stem Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1905))

Abstract

Lineage tracing of liver cells is a powerful tool to understand liver embryonic development, healthy liver cell homeostasis, tissue repair, and regeneration. Lineage tracing of biliary epithelial cells (BECs) in the adult liver has been used to assess the contribution of the biliary epithelium to liver injury, regeneration, and disease. These studies have shown the contribution of BECs to the expansion of ductular reaction (DR) and liver progenitor cells (LPCs) and eventually the generation of new hepatocytes. Few genetic lineage-tracing mouse models have been proved to trace BECs. This chapter is focused on lineage tracing of BECs in mouse models of liver injury and regeneration. First, we mention different existing approaches to trace the biliary epithelium based on proteins specifically expressed by BECs such as sex-determining region Y-box 9 (SOX9), osteopontin (OPN), and cytokeratin-19 (KRT19). Second, we describe mouse models that can be used to evaluate cell fate during liver injury and regeneration (i.e., partial hepatectomy (PHx), acute liver injury models, and chronic liver damage models such as 3,5-diethoxycarbonyl-1,4-dihydro-collidin (DDC) diet, choline-deficient ethionine-supplemented (CDE) diet, or chronic carbon tetrachloride (CCl4) administration). Third, we suggest possible readouts to assess BECs fate based on immunofluorescence analysis.

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Acknowledgments

We want to thank Daniel Rodrigo-Torres for the advice during manuscript preparation and the experimental work that this chapter is based on. This work was supported by grants from the Fondo de Investigación Sanitaria Carlos III (FIS), co-financed by the Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, “Una manera de hacer Europa” (FIS PI14/00320, PI 17/00673 to PS-B). PS-B and BA-B are funded by the Instituto de Salud Carlos III, Miguel Servet (CPII16/00041) and PFIS, respectively, and co-financed by the Fondo Europeo de Desarrollo Europeo (FEDER), Unión Europea, “Una manera de hacer Europa.”

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Authors and Affiliations

  1. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Teresa Rubio-Tomás, Beatriz Aguilar-Bravo & Pau Sancho-Bru

  2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain

    Pau Sancho-Bru

Authors
  1. Teresa Rubio-Tomás
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  2. Beatriz Aguilar-Bravo
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  3. Pau Sancho-Bru
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Corresponding author

Correspondence to Pau Sancho-Bru .

Editor information

Editors and Affiliations

  1. Sapporo Medical University, Sapporo, Hokkaido, Japan

    Naoki Tanimizu

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Rubio-Tomás, T., Aguilar-Bravo, B., Sancho-Bru, P. (2019). Genetic Lineage Tracing of Biliary Epithelial Cells. In: Tanimizu, N. (eds) Hepatic Stem Cells . Methods in Molecular Biology, vol 1905. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8961-4_5

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  • DOI: https://doi.org/10.1007/978-1-4939-8961-4_5

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8960-7

  • Online ISBN: 978-1-4939-8961-4

  • eBook Packages: Springer Protocols

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