[The precursor hematopoietic cell: its origin in ontogeny, proliferative activity and proliferative potential]

Abstract

Cells responsible for repopulation of irradiated longterm cultures of murine bone marrow and capable of generating CFUs for at least 4-5 weeks after seeding referred here to as primitive hemopoietic stem cells (P-HSC) were assayed by limiting dilution analysis. During development of mice P-HSC can be detected for the first time in the liver of 12-13-day-old embryos and their number is about 10 per organ. At day 17-18 of gestation the number of P-HSC increases ten-fold; however, we could not detect the proliferation of these cells using the technique of hydroxyurea suicide. In the adult mouse P-HSC content is about 100 precursors per femur and their concentration is one P-HSC per 1-2 x 10(5) bone marrow cells. P-HSC content in the spleen is 0.5 per 10(6) cells. In vivo treatment with 5-fluorouracil or hydroxyurea (six injections every 6 h) does not alter significantly the number of P-HSC, although either treatment kills about 99% of CFUs. Several months after reconstitution of lethally irradiated mice with a "small" inoculum of bone marrow cells (0.20-0.35 x 10(6)) the number of bone marrow P-HSC was reduced as compared to that in animals reconstituted by injection of a "large" cell dose (20-35 x 10(6)). These data suggest that P-HSC have limited proliferative potential and are incapable of self-maintenance.