IDENTIFICATION OF A LINEAGE OF MULTIPOTENT HEMATOPOIETIC PROGENITORS

All multipotent hematopoietic progenitors in C57BL-Thy-l.l bone marrow are divided among three subpopulations of Thy-1.1(lo)Sca-l(+)Lin(-/lo )c-kit(+) cells: long-term reconstituting Mac-l(-)CD4(-)c-kit(+) cells and transiently reconstituting Mac-1(lo)CD4(-) or Mac-1(lo)CD4(lo) ce lls. This study shows that the same populations, with similar function al activities, exist in mice whose hematopoietic systems were reconsti tuted by hematopoietic stem cells after lethal irradiation, We demonst rate that these populations form a lineage of multipotent progenitors from long-term self-renewing stem cells to the most mature multipotent progenitor population, In reconstituted mice, Mac-l(-)CD4(-)c-kit(+) cells gave rise to Mac-1(lo)CD4(-) cells, which gave rise to Mac-1(lo) CD4(lo) cells. Mac-l(-)CD4(-)c-kit(+) cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 1 0(4) functionally similar Mac-l(-)CD4(-)c-kit(+) cells, At least half of Mac-1(lo)CD4(-) cells had transient self-renewal potential, detecte d in the spleen 7 days after reconstitution, Mac-1(lo)CD4(lo) cells di d not have detectable self-renewal potential, The identification of a lineage of multipotent progenitors provides an important tool for iden tifying genes that regulate self-renewal and lineage commitment.