Classes of primitive murine megakaryocytic progenitor cells

We describe high proliferative potential colony-forming cells-megakaryocyte (HPP-CFU-Mk) from mouse bone marrow preparations using known cytokine combinations. These primitive precursors, which generate at least 80 megakaryocytes per colony, were detected from bone marrow populations enriched for primitive cells, either following treatment with 5-fluorouracil (5-FU) or after enrichment from normal bone marrow using immunological procedures. HPP-CFU-Mk were most reproducibly grown in the presence of interleukin-1 (IL-1) plus IL-3 plus IL-6, and mostly grew as a single large aggregate, rarely forming multiple foci. Cell separation studies showed that the HPP-CFU-Mk have membrane properties that characterized these cells as being intermediate between high proliferative myeloid primitive progenitors (high proliferative colony-forming cells [HPP-CFC]) and committed megakaryocyte progenitors (CFU-Mk). The data show that HPP-CFU-Mk can be designated as primitive cells on the basis of their being spared in vivo after 5-FU treatment, their proliferative potential to produce megakaryocytes, and their cofractionation with a proportion of primitive myeloid progenitor cells.