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

First Author  Sekiya S Year  2014
Journal  Am J Pathol Volume  184
Issue  5 Pages  1468-78
PubMed ID  24594350 Mgi Jnum  J:208140
Mgi Id  MGI:5561162 Doi  10.1016/j.ajpath.2014.01.005
Citation  Sekiya S, et al. (2014) Hepatocytes, rather than cholangiocytes, can be the major source of primitive ductules in the chronically injured mouse liver. Am J Pathol 184(5):1468-78
abstractText  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.
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