ABSTRACT
During the development from pluripotent stem cells to the mature progeny, the cells gradually become more and more lineage-restricted and lose the ability for self-renewal. Colony assays in semisolid medium have been extremely useful for studies of hematopoietic progenitor cells. Each colony represents the result of proliferation and differentiation of a single progenitor cell, and the phenotype of the mature colony reflects the potential of this cell to develop into cells of the various lineages, depending on the growth factors added (6,7). In such assays, committed cells which can give rise to cells of single lineages can be detected. These are named after the cell type of the colonies obtained, e.g., colony-forming unit-granulocyte (CFU-G). In addition, more multipotent cells giving rise to colonies with cells of different lineages can be detected (GFU-GM, CFU-GEMM, and CFU-mix). In general, multipotent cells are more immature than unipotent lineage-restricted cells. The most immature progenitor cells do not grow in standard colony assays and as a rule require a stromal support for growth in vitro (6, 7). The earliest cells that can be detected by in vitro culture are the long-term culture initiating cells (LTC-ICs), the high proliferative potential cells (HPPs), and the blast colony-forming cells (Bl-CFCs) (7, 44--47). However, at present the only assays for the most pluripotent stem cells are in vivo assays in animals (7,48). A schematic drawing of hematopoietic differentiation in relation to the various assay systems is shown in Figure 2.
