Analyses of cell surface molecules on hepatic stem/progenitor cells in mouse fetal liver.
OBJECTIVE
Hepatic stem/progenitor cells possess active proliferative ability and the capacity for differentiation into hepatic and cholangiocytic lineages. Our group and others have shown that a prospectively defined population in mid-gestational fetal liver contains hepatic stem/progenitor cells. However, the phenotypes of such cells are incompletely elucidated. We analyzed the profile of cell-surface molecules on primary hepatic stem/progenitor cells.


METHODS
Expression of cell surface molecules on primary hepatic stem/progenitor cells in mouse mid-gestational fetal liver was analyzed using flow cytometric multicolor analyses and colony-formation assays. The potential of the cells for liver repopulation was examined by transplantation assay.


RESULTS
We found that CD13 (aminopeptidase N) was detected on the cells of the previously reported (Dlk/Pref-1(+)) hepatic stem/progenitor fraction. Colony-formation assays revealed that the CD13(+) fraction, compared with the Dlk(+) fraction, of non-hematopoietic cells in fetal liver was enriched in hepatic stem/progenitor cells. Transplantation assay showed the former fraction exhibited repopulating potential in regenerating liver. Moreover, flow cytometric analysis for over 90 antigens demonstrated enrichment of hepatic stem/progenitor cells using several positive selection markers, including (hitherto unknown) CD13, CD73, CD106, and CD133.


CONCLUSIONS
Our data indicated that CD13 is a positive selection marker for hepatic stem/progenitor cells in mid-gestational fetal liver.
Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 1088639, Japan.
Sei
S
Kakinuma
Haruhiko
H
Ohta
Akihide
A
Kamiya
Yuji
Y
Yamazaki
Tsunekazu
T
Oikawa
Ken
K
Okada
Hiromitsu
H
Nakauchi
D015720:5'-Nucleotidase / Q000032:analysis; D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers; D001789:Blood Group Antigens / Q000032:analysis; D018826:CD13 Antigens / Q000032:analysis*; D006023:Glycoproteins / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D017493:Leukocyte Common Antigens / Q000032:analysis; D008099:Liver / Q000166:cytology* / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000032:analysis; D013234:Stem Cells / Q000737:chemistry*; D060225:Tetraspanin 28
D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D001789:Blood Group Antigens; C554798:CD81 protein, human; C554799:Cd81 protein, mouse; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; C489122:TER-119 antigen, mouse; D060225:Tetraspanin 28; D018799:Intercellular Adhesion Molecule-1; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human; D015720:5'-Nucleotidase; D018826:CD13 Antigens