Stem cell factor and its receptor c-kit constitute an important signal
transduction system implicated in survival, proliferation, and differ
entiation of stem cells in hematopoiesis, gametogenesis, and melanogen
esis. In the present study we used both immunocytochemical methods and
Western analysis to demonstrate the presence of this cytokine/recepto
r system in both embryonic and adult rat Liver. Stem cell factor was p
resent in the ductular cells around the portal vein during the late em
bryonic stage of the liver. In the adult liver both bile ducts and bil
e ductules were positive for stem cell factor and c-kit. When the acti
vation of the liver stem cell compartment was induced by combining adm
inistration of acetylaminofluorene and partial hepatectomy, both stem
cell factor and c-kit were expressed in the infiltrating oval cell pop
ulation, but absent in the newly formed basophilic hepatocytes. Activa
tion of oval cell proliferation following administration of D-galactos
amine also produced a similar but less prominent increase in the level
of the stem cell factor. Our data suggest that the stem cell faetor/c
-kit signal transduction system is involved in the development of bile
ducts and that it may also be an important member of the growth facto
r/receptor systems associated with the biology of liver stem cells. (C
) 1996 Academic Press, Inc.