A transmembrane glycoprotein, gp38, is a novel marker for immature hepatic progenitor cells in fetal mouse livers

In Vitro Cell Dev Biol Anim. 2011 Jan;47(1):45-53. doi: 10.1007/s11626-010-9354-7. Epub 2010 Nov 20.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism*
  • Bromodeoxyuridine
  • DNA Primers / genetics
  • Fetus / cytology*
  • Flow Cytometry
  • Keratin-19 / metabolism
  • Liver / cytology*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / metabolism*
  • Tetrazolium Salts
  • Thiazoles
  • Wnt Proteins / metabolism
  • Wnt3 Protein
  • Wnt3A Protein
  • alpha-Fetoproteins / metabolism

Substances

  • Biomarkers
  • DNA Primers
  • Gp38 protein, mouse
  • Keratin-19
  • Membrane Glycoproteins
  • Tetrazolium Salts
  • Thiazoles
  • Wnt Proteins
  • Wnt3 Protein
  • Wnt3A Protein
  • Wnt3a protein, mouse
  • alpha-Fetoproteins
  • thiazolyl blue
  • Bromodeoxyuridine