The sequential determination model of hematopoiesis

Analysis of hematopoietic development has for decades been central to understanding lineage diversification. Some models consider hematopoietic commitment to be random, and branching lineage maps often include an early myeloid or lymphoid bifurcation. However, the existence of joint lymphoid or myeloid intermediate progenitors argues against both. One of us earlier proposed the sequential determination (SD) model, which features a limited and stepwise set of binary choices across the full hematopoietic spectrum. This model arose from observations that hematopoietic progenitors show preferences for particular associations of lineage potentials – indicating that these linked fates are neighbours developmentally. An updated SD model complemented by several recently recognized processes – spatiotemporal fluctuations in transcription factor concentrations, asymmetric cell division, and Notch signalling – still offers a sound summary of hematopoiesis.