Hepatocytes, rather than cholangiocytes, can be the major source of primitive ductules in the chronically injured mouse liver

Sayaka Sekiya, Atsushi Suzuki

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)

Abstract

The proliferation of biliary lineage cells in chronic liver diseases, which leads to formation of primitive ductules in portal areas of the hepatic lobule, may be important not only for liver regeneration, but also for initiation of liver cancer. Thus, understanding how these primitive ductular cells emerge and proliferate in chronically injured liver holds promise for development of therapeutic strategies for liver diseases. However, the origin of these primitive ductular cells remains controversial. Here, we use a method for genetic lineage tracing to determine the origin of cells that form primitive ductules in a mouse model of chronic liver injury. Our results show that hepatocytes, rather than cholangiocytes, are the major source of cells for the primitive ductules formed in response to chronic liver damage. Moreover, activation of the Notch-Hes1 signaling axis is important for conversion of hepatocytes into primitive ductular cells in chronically injured liver. These findings should be valuable in elucidating the mechanism of liver regeneration associated with the fate-conversion of hepatocytes and in developing therapeutic strategies for liver diseases.

Original languageEnglish
Pages (from-to)1468-1478
Number of pages11
JournalAmerican Journal of Pathology
Volume184
Issue number5
DOIs
Publication statusPublished - May 2014

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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