Regulation of haematopoietic stem cell proliferation by stimulatory factors produced by murine fetal and adult liver.

Haematopoietic stem cells in murine fetal liver are in a proliferative state unlike those in normal bone marrow which are quiescent. A regulatory activity is produced by cells in the fetal liver which will switch quiescent normal bone marrow haematopoietic stem cells into cell cycle in vitro. This regulator from Day 15 fetal liver cells is produced by adherent cells and by cells fractionated on a Percoll gradient in the 1.064 and 1.076 g per cm3 density bands but not in the 1.123 g per cm3 band. Colony-stimulating factor cannot be detected in the supernatants containing the stem cell regulatory activity. The stimulator can be detected in supernatants produced from cell suspensions of liver cells at Day 15 and Day 17 of gestation and 24 hours and 72 hours after birth. However by 1 week after birth the production of the stimulator decreases and is undetectable 3 and 10 weeks after birth. The total numbers of haematopoietic stem cells (CFU-S) in fetal liver decrease from Day 15 of gestation and only small numbers are present 1 week after birth. Thus the decline in the production of haematopoietic stem cell proliferation stimulator correlates with the decrease in haematopoietic stem cell numbers in the liver through gestation and after birth.