Lineage Tracing Reveals the Bipotency of SOX9 + Hepatocytes during Liver Regeneration

Stem Cell Reports. 2019 Mar 5;12(3):624-638. doi: 10.1016/j.stemcr.2019.01.010. Epub 2019 Feb 14.

Abstract

Elucidation of the role of different cell lineages in the liver could offer avenues to drive liver regeneration. Previous studies showed that SOX9+ hepatocytes can differentiate into ductal cells after liver injuries. It is unclear whether SOX9+ hepatocytes are uni- or bipotent progenitors at a single-cell level during liver injury. Here, we developed a genetic tracing system to delineate the lineage potential of SOX9+ hepatocytes during liver homeostasis and regeneration. Fate-mapping data showed that these SOX9+ hepatocytes respond specifically to different liver injuries, with some contributing to a substantial number of ductal cells. Clonal analysis demonstrated that a single SOX9+ hepatocyte gives rise to both hepatocytes and ductal cells after liver injury. This study provides direct evidence that SOX9+ hepatocytes can serve as bipotent progenitors after liver injury, producing both hepatocytes and ductal cells for liver repair and regeneration.

Keywords: bipotent progenitors; clonal analysis; intersectional genetic strategy; lineage tracing; liver repair and liver regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Lineage / physiology*
  • Hepatocytes / metabolism*
  • Hepatocytes / physiology*
  • Homeostasis / physiology
  • Liver / metabolism*
  • Liver / physiology*
  • Liver Diseases / metabolism
  • Liver Diseases / pathology
  • Liver Regeneration / physiology*
  • Mice
  • SOX9 Transcription Factor / metabolism*

Substances

  • SOX9 Transcription Factor
  • Sox9 protein, mouse