BFU-E self-renewal: The probability of erythroid progenitor self-renewal versus differentiation depends on extrinsic and intrinsic factors. BFU-E progenitors either self-renew or differentiate depending on the body's need for generation of CFU-E and Epo-dependent erythroblasts. Although BFU-E self-renewal is very limited during steady-state erythropoiesis in the bone marrow, it is virtually limitless in the spleen during conditions of stress erythropoiesis. The cytokines Scf, Bmp4, and Shh promote self-renewal in addition, as does stimulation by GCs and hypoxia. These signals activate transcription factors Myc, Smad5, Scl, Gata2, Myb, and Hif1a.