Regulators of stem cell proliferation in the haemopoietic tissues of W/Wv and S1/S1d mice.

The presence of CFU-S proliferation stimulatory and inhibitory activities in the bone marrow and spleens of normal mice (+/+) and mice with mutations affecting the proliferative behaviour of stem cells (S1/S1d and W/Wv) has been investigated. S1/S1d and +/+ bone marrow and spleen contain virtually no detectable stimulator but the corresponding tissues from W/Wv mice are both strongly stimulatory. S1/S1d marrow in particular, but also +/+ marrow are strongly inhibitory whilst +/+ spleen, S1/S1d spleen, W/Wv marrow and W/Wv spleen all contain inhibitory activity but at a lower specific activity. The data are compatible with studies of cell and tissue grafts that have indicated an intrinsic haemopoietic stem cell defect in W/Wv mice and an extrinsic, microenvironmental defect in S1/S1d mice. It is suggested that they are also compatible with defective regulatory interactions between stem cells and regulator-producing cells and that the W and S1 loci may code for products involved in the production of, or response to, CFU-S proliferation regulators.