Identification of a lineage of multipotent hematopoietic progenitors

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Abstract
All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are divided among three subpopulations of Thy-1.1loSca-1+Lin−/loc-kit+cells:long-term reconstituting Mac-1−CD4−c-kit+ cells and transiently reconstituting Mac-1loCD4− or Mac-1loCD4lo cells. This study shows that the same populations, with similar functional activities, exist in mice whose hematopoietic systems were reconstituted by hematopoietic stem cells after lethal irradiation. We demonstrate 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-1−CD4−c-kit+ cells gave rise to Mac-1loCD4− cells, which gave rise to Mac-1loCD4lo cells. Mac-1−CD4−c-kit+ cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 104 functionally similar Mac-1−CD4−c-kit+ cells. At least half of Mac-1loCD4− cells had transient self-renewal potential, detected in the spleen 7 days after reconstitution. Mac-1loCD4lo cells did not have detectable self-renewal potential. The identification of a lineage of multipotent progenitors provides an important tool for identifying genes that regulate self-renewal and lineage commitment.