The high-proliferative-potential megakaryocyte mixed (HPP-Meg-Mix) cell: a trilineage murine hematopoietic progenitor with multiple growth factor responsiveness.

Megakaryocyte progenitors are notable for their response to synergistic cytokine combinations and apparently early position in the hematopoietic differentiation pathway. Although high-proliferative-potential murine megakaryocyte progenitors have been described, they have previously been primarily observed as unilineage colonies. We describe a subclass of agar-based high-proliferative-potential colony forming cells (HPP-CFC) derived from populations enriched for early hematopoietic progenitors which, when stimulated with the combination of CSF-1, G-CSF, GM-CSF, IL-1 alpha, IL-3 and SCF, produces colonies with trilineage potential for macrophages, granulocytes, and megakaryocytes. The high proliferative potential megakaryocyte mixed (HPP-Meg-Mix) colony-forming cell is defined as a cell meeting traditional criteria for HPP-CFC but additionally containing 20 or more megakaryocytes per colony. The combination of high-proliferative-potential, multilineage differentiation, and megakaryocytic lineage capacity suggests that the HPP-Meg-Mix marks a very early hematopoietic progenitor cell.