Developmental potential and dynamic behavior of hematopoietic stem cells.

We have used retrovirus-mediated gene transfer to mark hematopoietic stem cells in vitro and have tracked the fate of these cells after their transplantation into lethally irradiated recipients. Several classes of stem cells are demonstrated, including cells whose progeny completely repopulate all hematopoietic lineages as well as cells that contribute predominantly to certain lineages or to specific anatomical locations. In a majority of recipients, we find that few (1 or 2) stem-cell clones account for the majority of the mature hematopoietic cells. These results coupled with retransplantation studies suggest an in vivo mechanism for the temporal control of stem-cell use. Further studies based on periodic sampling of primary recipients suggest that normal hematopoiesis results from the sequential activation of different stem-cell clones rather than from an averaged contribution of the entire stem-cell pool.