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Progressive induction of hepatocyte progenitor cells in chronically injured liver.


ABSTRACT: Differentiated epithelial cells show substantial lineage plasticity upon severe tissue injuries. In chronically injured mouse livers, part of hepatocytes become Sry-HMG box containing 9 (Sox9) (+) epithelial cell adhesion molecule (-) hepatocyte nuclear factor 4 ? (+) biphenotypic hepatocytes. However, it is not clear whether all Sox9+ hepatocytes uniformly possess cellular properties as hepatocyte progenitors. Here, we examined the microarray data comparing Sox9+ hepatocytes with mature hepatocytes and identified CD24 as a novel marker for biphenotypic hepatocytes. Immunohistochemical analyses showed that part of Sox9+ hepatocytes near expanded ductular structures expressed CD24 in the liver injured by 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) diet and by bile duct ligation. Indeed, Sox9+ hepatocytes could be separated into CD24- and CD24+ cells by fluorescence activated cell sorting. The ratio of CD24+ cells against CD24- ones in Sox9+ hepatocytes gradually increased while DDC-injury progressed and colony-forming capability mostly attributed to CD24+ cells. Although hepatocyte markers were remarkably downregulated in of Sox9+ CD24+ hepatocytes, they re-differentiated into mature hepatocytes in vitro and in vivo. Our current results demonstrate that the emergence of biphenotypic hepatocytes is a sequential event including the transition from CD24- and CD24+ status, which may be a crucial step for hepatocytes to acquire progenitor properties.

SUBMITTER: Tanimizu N 

PROVIDER: S-EPMC5209740 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Progressive induction of hepatocyte progenitor cells in chronically injured liver.

Tanimizu Naoki N   Ichinohe Norihisa N   Yamamoto Masahiro M   Akiyama Haruhiko H   Nishikawa Yuji Y   Mitaka Toshihiro T  

Scientific reports 20170104


Differentiated epithelial cells show substantial lineage plasticity upon severe tissue injuries. In chronically injured mouse livers, part of hepatocytes become Sry-HMG box containing 9 (Sox9) (+) epithelial cell adhesion molecule (-) hepatocyte nuclear factor 4 α (+) biphenotypic hepatocytes. However, it is not clear whether all Sox9<sup>+</sup> hepatocytes uniformly possess cellular properties as hepatocyte progenitors. Here, we examined the microarray data comparing Sox9<sup>+</sup> hepatocyt  ...[more]

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