IDENTIFICATION OF A MURINE HIGH-PROLIFERATIVE-POTENTIAL COLONY-FORMING CELL (HPP-CFC) CAPABLE OF PRODUCING A NUMBER OF MEGAKARYOCYTES AND REPLATING FOR SECONDARY HPP-CFCS IN CULTURE

The high-proliferative-potential colony-forming cell (HPP-CFC) has bee n shown to be clearly heterogeneous. Hierarchical subpopulations can b e identified by analyzing the kinetics of cell regeneration and the sp ecific cellular requirement for cytokines. In this study, a new type o f HPP-CFC, termed high-proliferative potential mixed colony-forming un it-megakaryocyte (HPP-mCFU-MK), was detected in murine bone marrow cel l cultures. The HPP-mCFU-MK was able to form macroscopic colonies that fit the criteria of the HPP-CFC colony but contained a number of mega karyocytes. Its growth was stimulated by either aplastic anemia serum (AAS) or a combination of three or more recombinant hematopoietic grow th factors but was not inhibited by transforming growth factor-beta(1) (TGF-beta(1)) and platelet factor 4 (PF4) in vitro. The recloning of the 12-day-old HPP-mCFU-MK colonies picked up from AAS-stimulated prim ary cultures caused secondary formation of HPP-CFC colonies. These dat a suggest that HPP-mCFC-MK is a new subset of stem cell characterized by its ability to produce directly a number of megakaryocytes in respo nse to multifactor stimulation, to generate a secondary set of HPP-CFC in replating culture, and to be unaffected by TGF-beta(1) and PF4 tre atment.