title: Hepatocytes, rather than cholangiocytes, can be the major source of primitive ductules in the chronically injured mouse liver.
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.
authors.affiliation: Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Sekiya
authors.affiliation: Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi, Japan. Electronic address: suzukicks@bioreg.kyushu-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001652:Bile Ducts / Q000473:pathology* / Q000503:physiopathology; D002452:Cell Count; D019070:Cell Lineage; D002908:Chronic Disease; D004195:Disease Models, Animal; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology*; D018398:Homeodomain Proteins / Q000378:metabolism; D008099:Liver / Q000293:injuries* / Q000473:pathology* / Q000503:physiopathology; D017114:Liver Failure, Acute / Q000473:pathology / Q000503:physiopathology; D008115:Liver Regeneration; D008810:Mice, Inbred C57BL; D011725:Pyridines; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D000072056:Transcription Factor HES-1
chemical_list: D000418:Albumins; D051792:Basic Helix-Loop-Helix Proteins; D051557:Hepatocyte Nuclear Factor 4; D018398:Homeodomain Proteins; D011725:Pyridines; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C530773:3,5-diethoxycarbonyl-1,4-dihydrocollidine; C489734:Hes1 protein, mouse; C496593:Hnf4a protein, mouse