Regulation of murine granulocyte-macrophage progenitor cell and haemopoietic stem cell proliferation by factors produced in human fetal liver

At early stages (11–14 weeks) of gestation in human fetal liver few granulocyte-macrophage colony-forming cells (GM-CFC) are in DNA synthesis, whereas later in gestation (> 14 weeks) a large proportion of GM-CFC are in S-phase [Moore M.A.S. & Williams N. (1973) Cell Tissue Kinet.6, 461].Incubation of normal murine bone marrow GM-CFC (approx. 40% in DNA synthesis) with a supernatant from an early human fetal liver (11–14 weeks), reduced the proportion synthesizing DNA to <5%. In contrast, the proportion of murine GM-CFC synthesizing DNA was not affected by incubation with a supernatant from a late fetal liver (> 14 weeks).GM-CFC that had been switched out of cycle by incubation with a supernatant from an early gestation human fetal liver were switched back into cycle following incubation with a late human fetal liver supernatant.It is likely that changes in the relative levels of a proliferation inhibitor and stimulator throughout gestation might control the proportion of GM-CFC in cycle. In normal murine bone marrow (NMBM) approx. 10% of the haematopoietic stem cells (CFU-S) are synthesizing DNA. The proportion of CFU-S synthesizing DNA was increased to approx. 40% by incubation with a human fetal liver supernatant from all gestational ages tested (11–18 weeks).The specificity of these CFU-S and GM-CFC proliferation regulators is well demonstrated by an early gestation human fetal liver supernatant which will stimulate CFU-S proliferation but inhibit GM-CFC proliferation.The inhibitor and stimulator of GM-CFC proliferation are both produced by non-adherent human fetal liver cells. The GM-CFC proliferation inhibitor has a mol. wt of > 100,000 and the stimulator a mol. wt of 30,000–50,000. In contradistinction, the CFU-S proliferation stimulator is produced by adherent human fetal liver cells and has a mol. wt of 30,000–50,000.