Renewal and commitment to differentiation of hemopoietic stem cells (An interpretive review)

Abstract

In vivo and cell culture clonal assays provided quantitative assay methods for murine and human hemopoietic stem cells. Observations on the self-renewal and commitment of the hemopoietic stem cells during the past 2 decades may be summarized as follows. A structured hierarchy of multipotential hemopoietic stem cells assayable in culture and in vivo exists. The earliest stem cells have a high self-renewal capacity and are the most important in the establishment of a successful graft. The progenitors for stem (blast) cell colonies possess extensive self-renewal capacity and appear to be more primitive than the progenitors for macroscopic multilineage colonies (CFU-GEMM). Self-renewal and commitment to differentiation of the primitive hemopoietic stem cells appear to be governed by a stochastic rule, although the distributional parameter (p) may be under regulation of humoral factors. In contrast to an earlier model, the current model supports a more complex and multistep process of differentiation of multipotential to monopotential progenitors, i.e., progressive and stochastic loss of potencies. There is clinical and experimental evidence suggesting that T and B lymphocytes and hemopoietic cells are derived from a common progenitor. A schematic presentation of progenitors assayable in culture is shown in Fig. 1.