Normal and DBA erythropoiesis. (A) Adult erythropoiesis is a process by which single hematopoietic stem cells in the bone marrow differentiate and proliferate into billions of red blood cells. The figure shows a simplified scheme of the series of differentiation processes that takes place during red cell development. The main regulator of terminal erythropoiesis is Epo. Commonly used cell-surface markers that are used to enrich for the different progenitor populations are shown below the cells. (B) In patients with DBA the erythroid development is severely compromised. One convincing study localizes the erythroid defect to the Epo-dependent stages after the BFU-E stage.¹³  However, since there are reports of decreased BFU-E colony formation and decreased proliferation of multipotent progenitors in patients with DBA, it is possible that more primitive progenitors are affected as well.²⁶  (C) The expression of RPS19 is high in primitive progenitor cells and decrease in more mature erythroid cells. In contrast ribosome synthesis is low in primitive progenitors, whereas mature erythroid precursors have a very high rate of ribosome synthesis to meet the demand for globin synthesis. The illustration showing the timing of expression of erythroid transcription factors is a modified version of a figure by Anguita et al.⁸⁸  Epo indicates erythropoietin; HSC, hematopoietic stem cell; GEMM, granulocyte/erythrocyte/macrophage/megakaryocute colony-forming unit; BFU-E, erythrocyte burst-forming unit; CD34, positive cell-surface marker for hematopoietic progenitor cells; CD38, negative cell-surface marker for primitive hematopoietic progenitor cells; CD71, transferrin receptor; GlyA, glycophorin A.