Genetic Lineage Tracing of Biliary Epithelial Cells

  • Teresa Rubio-Tomás
  • Beatriz Aguilar-Bravo
  • Pau Sancho-BruEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1905)


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.

Key words

Lineage tracing Liver regeneration Biliary epithelial cells Liver progenitor cells Ductular reaction Chronic liver injury Animal models 



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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Teresa Rubio-Tomás
    • 1
  • Beatriz Aguilar-Bravo
    • 1
  • Pau Sancho-Bru
    • 1
    • 2
    Email author
  1. 1.Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)BarcelonaSpain
  2. 2.Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)BarcelonaSpain

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