Characterization and functional analyses of hepatic mesothelial cells in mouse liver development.
OBJECTIVE
At the onset of liver development, cardiac mesoderm, septum transversum mesenchyme, and endothelial cells are involved in the specification and/or proliferation of hepatoblasts. After this initial stage, however, it is unclear which cells support the proliferation and differentiation of hepatocytes. Here we characterized the nature of mouse hepatic mesothelial cells (MCs) and investigated their role in organogenesis.


METHODS
Using anti-podocalyxin-like protein 1 (PCLP1) and anti-mesothelin antibodies, we characterized MCs during liver development by immunohistochemistry, flow cytometry, and gene expression analysis. The possible role of MCs in hepatogenesis was investigated by in vitro culture and analysis of Wilms' tumor 1 homologue (WT1) knockout mice.


RESULTS
PCLP1 was highly expressed in immature MCs, covering the surface of lobes. PCLP1 expression in MCs was down-regulated along with development, whereas mesothelin expression was up-regulated, indicating that these molecules distinguished developmental stages of MCs. The proliferation potential of MCs was high in the fetus and declined after birth. Fetal MCs expressed various growth factors and strongly enhanced the expansion of fetal hepatocytes in vitro, whereas differentiated MCs exhibited less growth factor expression, and differentiated MCs failed to enhance hepatocyte proliferation in vitro. In WT1-deficient embryos, hepatocyte proliferation was impaired due to defective MCs.


CONCLUSIONS
The mesothelium is not only an inert protective sheet covering the parenchyma but also changes its characteristics dynamically during development and plays an active role in organogenesis by promoting expansion of parenchymal cells.
Onitsuka
Izumi
I
Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
Tanaka
Minoru
M
Miyajima
Atsushi
A
D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology*; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D022781:Hepatocytes / Q000502:physiology*; D008099:Liver / Q000196:embryology*; D008562:Membrane Glycoproteins / Q000032:analysis; D000090204:Mesothelin; D051379:Mice; D008810:Mice, Inbred C57BL; D012795:Sialoglycoproteins / Q000032:analysis; D025721:WT1 Proteins / Q000502:physiology
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C000715528:Msln protein, mouse; D012795:Sialoglycoproteins; D025721:WT1 Proteins; C001643:podocalyxin; D000090204:Mesothelin