title: A transmembrane glycoprotein, gp38, is a novel marker for immature hepatic progenitor cells in fetal mouse livers.
abstract: Previously, we clarified the surface antigen profiles of hepatic progenitor cells (HPCs) in fetal liver tissue as the CD49f(+)CD45(-)Thy1(-) cell fraction. However, these cells were a heterogeneous cell population containing various stages of differentiation. This study aimed to detect more immature HPCs, using a novel surface antigen, gp38. After the collagenase digestion of fetal livers harvested from E13.5 to E18.5 fetal mice, HPCs were obtained and divided into two subpopulations using flow cytometry: gp38-positive HPCs, and gp38-negative HPCs. Both types of HPCs were characterized by immunocytochemistry and RT-PCR. The proliferative activity was compared by BrdU incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTS) assay. Furthermore, the comprehensive gene expression was investigated by DNA microarray. Both types of HPCs expressed alpha-fetoprotein. However, the gp38-positive HPCs derived from E13.5 fetal livers did not express albumin or cytokeratin 19, while the gp38-negative HPCs did. DNA microarray revealed that some genes related to the Wnt signal pathway were up-regulated in the gp38-positive HPCs. Furthermore, Wnt3a had a proliferative effect on the gp38-positive HPCs. In conclusion, the gp38-positive HPCs derived from fetal liver tissue until E13.5 could therefore be candidates for hepatic stem cells in the fetal liver.
authors.affiliation: Department of Surgery, Graduate School of Medicine Kyoto University, 54 Kawahara-cho Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Konishi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yasuchika
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ishii
authors.forename: Ken
authors.initials: K
authors.lastname: Fukumitsu
authors.forename: Naoko
authors.initials: N
authors.lastname: Kamo
authors.forename: Naoya
authors.initials: N
authors.lastname: Fujita
authors.forename: Iwao
authors.initials: I
authors.lastname: Ikai
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001973:Bromodeoxyuridine; D017931:DNA Primers / Q000235:genetics; D005333:Fetus / Q000166:cytology*; D005434:Flow Cytometry; D053539:Keratin-19 / Q000378:metabolism; D008099:Liver / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D051153:Wnt Proteins / Q000378:metabolism; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D000509:alpha-Fetoproteins / Q000378:metabolism; D000098853:Podoplanin
chemical_list: D015415:Biomarkers; D001973:Bromodeoxyuridine; D017931:DNA Primers; D053539:Keratin-19; D008562:Membrane Glycoproteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D000509:alpha-Fetoproteins; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C555511:Wnt3a protein, mouse; C022616:thiazolyl blue