A model for the effect of stress on the hematopoietic compartments in the presence of wild-type GATA1 and GATA2 genes or in the presence of loss-of-function GATA1 and GATA2 mutations. In vitro models of stress erythropoiesis indicate that the stress signal increases the erythroid output by amplifying the hematopoietic progenitor cell compartments (HPCs) through increased levels of GATA2 expression.¹⁶  Surprisingly, in spite of the purity of CD34^pos populations used to start the culture and the exclusively erythroid-permissive culture conditions used, macrophages are always detected in these cultures and erythroblastic-island–like structures (inset, kindly provided by Migliaccio laboratory) are frequently observed on smears prepared with erythroid cells expanded under stress conditions. In the presence of GATA1^mut, which impairs the maturation potential of the precursor compartments, stress must induce an even greater expansion of the HPC compartment leading to the development of myeloproliferative neoplasms (MPNs)^8,16 ; however, the amplification potential of the HPCs is sufficient to increase the precursor cell demand necessary to respond to stress, leaving the hematopoietic stem cell compartment (HSC) unstimulated. In contrast, the presence of a loss-of-function GATA2 mutation hampers HPC proliferation, reducing in turn the numbers of precursor cells generated by the HPCs. An effective response to the increased precursor cell demand induced by stress requires the generation of new HPCs from the HSC compartment, resulting, if the stress is prolonged, in HSC exhaustion and MDS. Professional illustration by Debra T. Dartez.