Making the Choice: The importance of cytokine signals for the generation of specific blood lineages is well known. However, whether cytokines only influence survival and proliferation of cells that have already committed to one lineage, or if they also influence the lineage choice is unclear. For decades, researchers disputed whether lineage choice of hematopoietic progenitor cells be influenced by cell extrinsic cytokines. Using bioimaging approaches that allow long-term observation of all cells in progenitor cell cultures, Rieger et al. (p. 217 ) now demonstrate that certain cytokines can indeed instruct blood lineage choice.

Enormous numbers of adult blood cells are constantly regenerated throughout life from hematopoietic stem cells through a series of progenitor stages. Accessibility, robust functional assays, well-established prospective isolation, and successful clinical application made hematopoiesis the classical mammalian stem cell system. Most of the basic concepts of stem cell biology have been defined in this system. At the same time, many long-standing disputes in hematopoiesis research illustrate our still limited understanding. Here we discuss the embryonic development and lifelong maintenance of the hematopoietic system, its cellular components, and some of the hypotheses about the molecular mechanisms involved in controlling hematopoietic cell fates.