Nj. Drize et al., LOCAL CLONAL ANALYSIS OF THE HEMATOPOIETIC SYSTEM SHOWS THAT MULTIPLESMALL SHORT-LIVING CLONES MAINTAIN LIFELONG HEMATOPOIESIS IN RECONSTITUTED MICE, Blood, 88(8), 1996, pp. 2927-2938
We describe here a technique to study the clonal contribution of primi
tive stem cells that account for long-term hematopoiesis in the same m
ouse over a 14-month period. Specifically, irradiated recipient female
mice were transplanted with retrovirally marked male hematopoietic pr
ogenitors. Bone marrow was then collected repeatedly from local sites
from the same mice throughout a 14-month period and injected into seco
ndary irradiated recipients for analysis of donor retrovirally marked
day-ii colony-forming unit-spleen (CFU-S-11). We have tracked the temp
oral in vivo fate of 194 individual CFU-S-derived cell clones in 38 mi
ce reconstituted with such retrovirally marked bone marrow cells. Our
data show that long-term hematopoiesis is maintained by a large number
of simultaneously functioning small, short-lived (1 to 3 months) clon
es that usually grow locally with little or no dispersion between diff
erent regions of the hematopoietic system, Furthermore, the clones tha
t disappeared were never detected again. The data suggest that normal
hematopoiesis is supported by the sequential recruitment of marrow rep
opulating cells into a differentiation mode. (C) 1996 by The American
Society of Hematology.