Thy1-positive cells have bipotential ability to differentiate into hepatocytes and biliary epithelial cells in galactosamine-induced rat liver regeneration.
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.
Kon
Junko
J
Department of Pathophysiology, Cancer Research Institute, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan. junko.kon@ucsf.edu
Ichinohe
Norihisa
N
Ooe
Hidekazu
H
Chen
Qijie
Q
Sasaki
Kazunori
K
Mitaka
Toshihiro
T
D000818:Animals; D001659:Biliary Tract / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D002469:Cell Separation; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D005688:Galactosamine / Q000633:toxicity; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism*
D018960:Hyaluronan Receptors; D018800:Thy-1 Antigens; D005688:Galactosamine