Stem cell factor induces proliferation and differentiation of fetal progenitor cells in the mouse.
We have investigated the kinetics of the amplification of the progenitor cell compartments (CFC) in haemopoietic organs during murine ontogenesis and compared the growth requirements of fetal and adult CFC. Two haemopoietic phases were recognized in the fetal liver (FL): an exponential 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 increased from 4.9 x 10(5) to 7.0 x 10(7) and from 4.5 x 10(3) to 2.7 x 10(5), respectively, and a recessive phase after 15.5 d p.c., during which the CFC number in the FL gradually decreased, although some CFC were still detectable in the liver after birth. In serum-deprived cultures, FL and adult 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 numbers of erythroid bursts from FL, but not from AM cells. The proliferative and differentiative effect of SCF alone on fetal cells was confirmed in serum-deprived cultures of purified early progenitor cells isolated by cell sorting on the basis of multiple parameters from FL and AM light-density cells. In culture of purified FL cells, SCF alone induced a similar amplification of total cells (maximal amplification at day 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 amplification of total cells and 31-88-fold amplification of CFC). In contrast, SCF alone allowed only survival of purified AM early progenitor cells. Therefore FL early progenitor cells have an intrinsic higher potential than their adult counterpart to respond to SCF, confirming the potent role of this growth factor in the development of the murine haemopoietic system.
Laboratory of Hematopoietic Growth Factors, Lindsley F. Kimball Research Institute, New York Blood Center, New York, USA.
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D000818:Animals; D001853:Bone Marrow / Q000196:embryology; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development; D004921:Erythropoietin / Q000502:physiology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007377:Interleukin-3 / Q000494:pharmacology; D008099:Liver / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D019089:Stem Cell Factor / Q000494:pharmacology*
D007377:Interleukin-3; D019089:Stem Cell Factor; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor