Regulation of haemopoietic stem‐cell proliferation in mice carrying the Slj allele

We investigated a haemopoietic stromal defect, in mice heterozygous for the Slj allele, during haemopoietic stress induced by treatment with bacterial lipopolysaccharides (LPS) or lethal total body irradiation (TBI) and bone‐marrow cell (BMC) reconstitution. Both treatments resulted in a comparable haemopoietic stem cell (CFU‐s) proliferation in Slj/+ and +/+ haemopoietic organs. There was no difference in committed haemopoietic progenitor cell (BFU‐e and CFU‐G/M) kinetics after TBI and +/+ bone‐marrow transplantation in Slj/+ and +/+ mice. the Slj/+ mice were deficient in their ability to support macroscopic spleen colony formation (65% of +/+ controls) as measured at 7 and 10 days after BMC transplantation. However, the Slj/+ spleen colonies contained the same number of BFU‐E and CFU‐G/M as colonies from +/+ spleens, while their CFU‐s content was increased. On day 10 post‐transplantation, the macroscopic ‘missing’ colonies could be detected at the microscopic level. These small colonies contained far fewer CFU‐s than the macroscopic detectable colonies. Analysis of CFU‐s proliferation‐inducing activities in control and post‐LPS sera revealed that Slj/+ mice are normal in their ability to produce and to respond to humoral stem‐cell regulators. We postulate that Slj/+ mice have a normal number of splenic stromal ‘niches’ for colony formation. However, 35% of these niches is defective in its proliferative support. Copyright

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