Self-renewal of stem cells.

The mechanisms that regulate the fate of hematopoietic stem cells are poorly understood. Hematopoietic growth factors and factors in the microenvironment are clearly essential for ensuring the survival and differentiation of hematopoietic stem cells, but their role in the selection between self-renewal and lineage commitment options is unclear. Differences in the functional behavior of purified stem cells at different stages of development suggest that developmentally-regulated intrinsic factors may play an important role in directing stem cell fate. Recent studies strongly implicate homeobox genes in these processes and have further emphasized the link between developmental and stem cell biology. Changes in stem cell function during development correlate with measurable changes in telomere length, and loss of telomere repeats may limit the replicative potential of stem cells. In order to reconcile developmental changes in stem cell properties with loss of telomeric DNA, the intrinsic timetable model of stem cell biology is introduced. In this model, the self-renewal properties of stem cells are relative and their replicative potential is limited to less than 100 cell divisions.