| 19893024 |
Kon J, Ichinohe N, Ooe H, Chen Q, Sasaki K, Mitaka T: Thy1-positive cells have bipotential ability to differentiate into hepatocytes and biliary epithelial cells in galactosamine-induced rat liver regeneration. Am J Pathol. 2009 Dec;175(6):2362-71. Epub 2009 Nov 5.
In galactosamine (GalN)-induced rat liver injury, hepatic stem/progenitor cells, small hepatocytes (SHs) and oval cells, transiently appear in the initial period of liver regeneration. To clarify the relationship between SHs and oval cells, CD44 (+) and Thy1 (+) cells were sorted from GalN-treated livers and used as candidates for SHs and oval cells, respectively. Some Thy1 (+) cells isolated 3 days after GalN-treatment (GalN-D3) formed CD44 (+) cell colonies, but those from GalN-D2 could form few. GeneChip (Affymetrix, Inc, Santa Clara, CA) analysis of the sorted cells and cultured Thy1 (+) cells suggested that hepatocytic differentiation progressed in the order Thy1 (+) (GalN-D3), Thy1 (+) cell colony (Thy1-C), and CD44 (+) (GalN-D4) cells. When Thy1 (+), Thy1-C, and CD44 (+) cells were transplanted into retrorsine/PH rat livers, they could proliferate to form hepatocytic foci. At 30 days after transplantation most cells forming the foci derived from CD44 (+) cells possessed C/EBPalpha (+) nuclei, whereas only a few cells derived from Thy1-C showed this positivity. When Thy1 (+) (GalN-D3) cells were cultured between collagen gels in medium with hepatocyte growth factor (+)/dexamethasone (-)/dimethyl sulfoxide (-), ducts/cysts consisting of biliary epithelial cells appeared, whereas with CD44 (+) and Thy1 (+) (GalN-D2) cells they did not. Taken together, these results indicate that the commitment of Thy1 (+) cells to differentiate into hepatocytes or biliary epithelial cells may occur between Day 2 and Day 3. Furthermore, some Thy1 (+) cells may differentiate into hepatocytes via CD44 (+) SHs. |
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