How do stem cells decide what to do?

The continuous replenishment of mature blood cells from multipotent stem cells proceeds under the influence of haemopoietic growth factors which clearly regulate both cell survival and proliferation. The extent to which these factors might influence lineage choice is still unclear, however, and it seems likely that resolution of this issue will require direct analysis of multipotent cells undergoing commitment rather than determination of their productivity in colony assays. Chromatin analysis of a multipotent progenitor cell line indicates that many of the genes relevant to alternative lineage fates are maintained in an accessible (primed) state prior to lineage commitment. Furthermore, multipotent cells have been found to co-express a number of lineage-restricted genes, suggesting that commitment proceeds as the consolidation of an existing programme. There are indications that the patterns of gene expression in multipotent progenitors change over time, raising the possibility of temporal priming towards different lineages. In multipotential cell lines, exogenous growth factors are necessary for survival, but not for lineage commitment, implying a largely supportive role in early progenitors. In contrast, recent work on primary bipotent granulocyte/ macrophage progenitors does demonstrate an inductive role for growth factors in these more lineage-restricted cells.