Model for permissive and instructive cytokine effects on HSPCs. (A) In the permissive model, HSPCs generate different lineage-committed progenitors (green and yellow) at intrinsically determined ratios, irrespective of external cues. Committed progenitors express lineage-specific cytokine receptors that transmit survival, proliferation, and maturation signals, resulting in selection of the appropriate progenitors and eventually biased lineage outcome (green), depending on the distinct cytokine milieu (green cytokine > yellow cytokine). (B) In the instructive model, unbiased HSPCs express different cytokine receptors specific for several lineages (green and yellow) and are instructed to differentiate to a lineage according to the cytokine milieu present (green cytokine > yellow cytokine).