Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes

Branden D. Tarlow, Carl Pelz, Willscott E. Naugler, Leslie Wakefield, Elizabeth M. Wilson, Milton J. Finegold, Markus Grompe

Research output: Contribution to journalArticle

243 Scopus citations

Abstract

Adult liver progenitor cells are biliary-like epithelial cells that emerge only under injury conditions in the periportal region of the liver. They exhibit phenotypes of both hepatocytes and bile ducts. However, their origin and their significance to injury repair remain unclear. Here, we used a chimeric lineage tracing system to demonstrate that hepatocytes contribute to the progenitor pool. RNA-sequencing, ultrastructural analysis, and in vitro progenitor assays revealed that hepatocyte-derived progenitors were distinct from their biliary-derived counterparts. In vivo lineage tracing and serial transplantation assays showed that hepatocyte-derived proliferative ducts retained a memory of their origin and differentiated back into hepatocytes upon cessation of injury. Similarly, human hepatocytes in chimeric mice also gave rise to biliary progenitors in vivo. We conclude that human and mouse hepatocytes can undergo reversible ductal metaplasia in response to injury, expand as ducts, and subsequently contribute to restoration of the hepatocyte mass.

Original languageEnglish (US)
Pages (from-to)605-618
Number of pages14
JournalCell Stem Cell
Volume15
Issue number5
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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