Nature 264, 68 - 69 (04 November 1976); doi:10.1038/264068a0

Haemopoietic stem cells are organised for use on the basis of their generation-age

MARTIN ROSENDAAL, G. S. HODGSON & T. R. BRADLEY

Biological Research Unit, Cancer Institute, 481 Little Lonsdale Street, Melbourne, 3000, Australia

THE spleen-colony assay of Till and McCulloch¹, which is a clonal assay², measures the content of haemopoietic cells in blood-forming tissues. Stem cells (colony forming units in spleen, CPUS) form red cells, granulocytes, platelets and themselves (self-renewal) in these colonies^3,4. Worton et al. ⁵ reported that stem cells separated by velocity sedimentation differed in their capacity for self-renewal. Schofield and Lajtha⁶ reported that CPUS from mice treated with iso-propyl methane sulphonate have a low self-renewal capacity. We have studied the functional capacity of myeloid stem cells from normal mice (NBM) and mice treated with hydroxyurea. CPUS from mice treated with five injections of hydroxyurea (5 HUBM, G.S.H. and N. M. Blackett, unpublished) formed 3 times more CPUS and 2.5 times more colony forming units in culture per original colony (CFUC, a committed precursor of granulopoiesis⁷) than those from NBM. When these grafted CPUS were retransplanted they still formed three times more CFUC and CPUS per secondary colony than those from NBM (Tables 1 and 2).

References

1.	Till, J. E., and McCulloch, E. A., Rad. Res., 14, 213–222 (1961).
2.	Becker, A. J., McCulloch, E. A., and Till, J. E., Nature, 197, 452–454 (1963).
3.	Fowler, J. H., Wu, A. M., Till, J. E., McCulloch, E. A., and Siminovitch, L., J. Cell Physiol., 69, 65–72 (1967).
4.	McCulloch, E. A., and Till, J. E., Rad. Res., 22, 383–397 (1963).
5.	Worton, R. G., McCulloch, E. A., and Till, J. E., J. exp. Med., 130, 91–103 (1969).
6.	Schofield, R., and Lajtha, L. G., Br. J. Haemat., 25, 195–202 (1973).
7.	Bradley, T. R., and Metcalf, D., Aust. J. exp. Biol. Med. Sci., 44, 287–300 (1966).
8.	Hodgson, G. S., Bradley, T. R., Martin, R. F., Sumner, M., and Fry, P., Cell Tissue Kinet., 8, 51–60 (1975).
9.	Hodgson, G. S., Bradley, T. R., and Telfer, P. A., Cell Tissue Kinet., 5, 283–288 (1972).