Megakaryocyte progenitors are notable for their response to synergisti
c cytokine combinations and apparently early position in the hematopoi
etic differentiation pathway. Although high-proliferative-potential mu
rine megakaryocyte progenitors have been described, they have previous
ly been primarily observed as unilineage colonies. We describe a subcl
ass of agar-based high-proliferative-potential colony forming cells (H
PP-CFC) derived from populations enriched for early hematopoietic prog
enitors which, when stimulated with the combination of CSF-1, G-CSF, G
M-CSF, IL-1 alpha, IL-3, and SCF, produces colonies with trilineage po
tential for macrophages, granulocytes, and megakaryocytes. The high pr
oliferative potential megakaryocyte mixed (HPP-Meg-Mix) colony-forming
cell is defined as a cell meeting traditional criteria for HPP-CFC bu
t additionally containing 20 or more megakaryocytes per colony. The co
mbination of high-proliferative-potential, multilineage differentiatio
n, and megakaryocytic lineage capacity suggests that the HPP-Meg-Mix m
arks a very early hematopoietic progenitor cell.