Figure 1.

Illustration of the human bone marrow cell restricted pathways of the differentiation of hematopoietic stem cells into mature blood cells. In the lower right box, the erythroid cell restricted lineage differentiation is shown. HSCs give rise to common myeloid progenitors (CMP) and common megakaryocyte erythroid progenitors (MEP). The latter are differentiated into erythropoietin-responsive BFU-E and CFU-E clones, shown by the arrows where human EPO acts upon them. Interactions of EPO with its homodimeric EPO-R lead to cell signaling activation pathways that increase the biosynthesis of hemoglobin. The levels of hemoglobins increase as erythropoiesis continues in the proerythroblasts, in the orthochomatic normoblasts (ON) and finally in the reticulocytes and mature red blood cells (RBCs) following the extrusion of the nucleus. Erythropoiesis is homeostatically regulated by low-oxygen conditions (hypoxia) and the final end production via a feedback action loop. The original figure was published by Tsiftsoglou et al. [4] and has been lightly modified accordingly to indicate where EPO acts upon in the proerythroid cells. The initial commitment to the erythroid cell lineage restricted pathway of differentiation begins at the level of BM HSCs and leads to the formation of MEPs that yield BFU-Es and CFU-Es. The most recently published work by Eisele et al. [9] provided direct evidence indicating that EPO indeed acts upon the BM HSCs to promote commitment towards the erythroid maturation.