Hemopoietic Stem and Progenitor Cells

Pluripotent hemopoietic stem cells (PHSC) 1 are operationally defined by their ability to generate all of the cellular components of the lymphohemopoietic system while retaining the capacity for extensive self-replication. The existence of PHSC has been documented by the in vivo spleen colony-forming unit (CFU-S) assay (1) and by cell tracer studies (2, 3). The major obstacles to the isolation of PHSC have been their paucity in hemopoietic tissues (4), their close physical similarities to myeloid and erythroid progenitor cells (5, 6), and the absence of a stem cell-specific isotypic marker (7). Myeloid progenitor cells are committed to differentiation along one or at most two pathways of leukocyte development. They can be identified and enumerated operationally by their ability to produce colonies of differentiated leukocytes in semisolid medium in the presence of specific colony-stimulating factors (CSF) (8). Consequently they are referred to as in vitro colony-forming cells (CFC). To date, progenitor cells have been identified for neutrophilic granulocytes ((3) and macrophages (M) (GMCFC), eosinophils (EO) (EO-CFC) and megakaryocytes (MEG) (MEG-CFC). Clusterforming cells, which produce small aggregates of G and /o r M in vitro, are thought to be progeny of GM-CFC. Single-cell transfer experiments have demonstrated the clonal origin of G and M (9). Results of subcloning studies have suggested that progenitors of G are ancestral to progenitors of M (10). This view has been reinforced by experiments in which developmentally discrete subsets of GM-CFC have been partially resolved by velocity sedimentation (11).