Haemopoietic stem cell proliferation in the bone marrow of S1/S1d mice.
In marrow from Sl/Sld mice (but not +/+ mice) day 7 and day 8 CFU-S proliferate whilst day 10 and day 12 CFU-S exhibit negligible proliferation. Media conditioned by both +/+ and Sl/Sld marrow contains an inhibitor of CFU-S proliferation but day 8 CFU-S in +/+ and Sl/Sld marrow show marked dose-response differences to this factor. To inhibit the proliferation of Sl/Sld CFU-S required approximately ten times the concentration of inhibitor that inhibited the proliferation of +/+ CFU-S. Thus abnormally responsive day 8-CFU-S were shown to proliferate in an inhibitory environment. Abnormalities in Sl/Sld CFU-S function were also demonstrated in heterotopic transplantation experiments using +/+ and Sl/Sld donors and hosts to obtain ectopic bone marrow with various stromal (donor) and haemopoietic (host) combinations. Day 8 Sl/Sld CFU-S were seen to proliferate, irrespective of whether the stromal environment was derived from Sl/Sld or +/+ marrow. Sl/Sld mice are generally regarded as animals in which there is a genetically determined defect in haemopoiesis due to an abnormality in the haemopoietic environment. It is difficult, however, to attribute the abnormal CFU-S behaviour in these experiments to environmental factors and the results are consistent with mutation at the Sl locus affecting the responses of CFU-S to regulatory signals, i.e. the genetic defect is not confined to the stromal environment.
Wright
E G
EG
Department of Anatomy and Experimental Pathology, University of St Andrews, Scotland.
Lorimore
S A
SA
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D010659:Phenylhydrazines / Q000494:pharmacology; D013997:Time Factors
D010659:Phenylhydrazines; C030299:phenylhydrazine