STEM-CELL FACTOR INDUCES PROLIFERATION AND DIFFERENTIATION OF FETAL PROGENITOR CELLS IN THE MOUSE

We have investigated the kinetics of the amplification of the progenit or cell compartments (CFC)in haemopoietic organs during murine ontogen esis and compared the growth requirements of fetal and adult CFC. Two haemopoietic phases were recognized in the fetal liver (FL): an expone ntial growth phase, from 11.5 to 15.5 d post conception (p.c.), during which the mean number of nucleated cells and of CFC in the FL increas ed from 4.9x10(5) to 7.0x10(7) and from 4.5x10(3) to 27x10(5) respecti vely, and a recessive phase after 15.5d p.c., during which the CFC num ber in the FL gradually decreased, although some CFC were still detect able in the liver after birth. In serum-deprived cultures, FL and adul t marrow (AM) CFC had similar responses to GM-CSF and did not respond to G-CSF or IL-3. In contrast, FL, but not AM, erythroid colonies grew Epo-independently whereas SCF alone induced formation of maximal numb ers of erythroid bursts from FL, but not from AM cells. The proliferat ive and differentiative effect of SCF alone on fetal cells was confirm ed in serum-deprived cultures of purified early progenitor cells isola ted by cell sorting on the basis of multiple parameters from FL and AM light-density cells. In culture of purified FL cells, SCF alone induc ed a similar amplification of total cells (maximal amplification at da y 12: 800-300-fold) and total CFC (11-38-fold of maximal amplification at day 6) to the combination of SCF plus IL-3 (1300-800-fold amplific ation of total cells and 31-88-fold amplification of CFC). In contrast , SCF alone allowed only survival of purified AM early progenitor cell s. Therefore FL early progenitor cells have an intrinsic higher potent ial than their adult counterpart to respond to SCF, confirming the pot ent role of this growth factor in the development of the murine haemop oietic system.