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Abstract
In order to introduce small numbers of stem cells whose proliferation and development could be easily followed, neonatal unirradiated W-mutant mice were used as hosts for fetal liver or bone marrow marked with biochemical markers or with retroviral integrations. W-mutants have a stem cell defect which confers a selective advantage on donor cells, and results in engraftment at the level of the defect without engraftment of cells at later stages of hematopoiesis. Repopulation depended upon H-2-compatibility, and the frequency and rate of engraftment characteristically diminished in the series W/W$\sp{v}$, W$\sp{f}$/W$\sp{f}$, and W$\sp{v}$/+, in which the severity of the defect decreases. Coculture of fetal liver or bone marrow to introduce viral integration markers reduced its overall engraftment efficiency, but after 24 hours of culture individual stem cells retained their ability to function normally. Under these conditions, engraftment in W/W$\sp{v}$ hosts was limited to a small number of hematopoietic stem cells whose clonal progeny were detected in all hematopoietic lineages, myeloid and lymphoid. Results demonstrated the concurrent contributions of cohorts of stem cells to hematopoiesis, and indicated that clones may wax and wane, disappear or appear after a long quiescent period. In any one tissue, a single clone represented 5-20% of the total hematopoietic contribution. Clonal histories were followed for more than $2{1\over2}$ years by transfer of bone marrow from primary to secondary and from secondary to tertiary hosts. The frequency with which stem cells of a single clone are distributed to each of numerous secondary or tertiary hosts defines a minimum concentration of members of that clone in total bone marrow and demonstrates the re-expansion of a stem cell clone in a secondary host. These experiments help to illuminate the structure of the hematopoietic stem cell compartment.
