Red blood cells (RBCs) transport oxygen to all body tissues. These cells survive only for 120 days and then need to be replenished. Erythropoiesis is the process of RBC production. In healthy individuals, erythropoiesis ensures all tissues are amply supplied with oxygen. In addition, blood loss due to injury leads to a drop in the physiological oxygen level that will cause erythropoiesis. Any defect in erythropoiesis leads to several physiological disorders, including thalassemia, anemia, and polycythemia.

Erythropoietin is a protein that (Epo) initiates erythropoiesis. The fetal liver initially produces Epo; however, post-birth, Epo is secreted by interstitial cells of the kidney. These cells sense a drop in physiological oxygen levels and induce Epo production.

As the level of Epo increases, Epo binds the erythropoietin receptor (EpoR) on erythroid progenitors. These progenitors reside in distinct niches called the “erythroblastic islands” of the bone marrow. Erythroid progenitors continue to proliferate and survive by interacting with a central macrophage or ‘nurse cells.’ Upon stimulation, these progenitors undergo a series of differentiation and maturation stages. The early erythroid called burst-forming unit-erythroid (BFU-E) differentiates into colony-forming unit-erythroid or CFU-E. The CFU-E then develops into a pro-erythroblast that eventually loses the nucleolus and forms the basophilic erythroblast. The basophilic erythroblast starts accumulating hemoglobin and matures into a polychromatic erythroblast. Polychromatic erythroblasts have a higher amount of hemoglobin and many ribosomes. Polychromatic erythroblasts develop into orthochromatic erythroblasts, characterized by a small dense nucleus and hemoglobin filing most of the volume of the cell. Once orthochromatic erythroblasts expel the nucleus and lose the organelles, they form immature reticulocytes that stay in bone marrow for 2-3 days before entering the bloodstream, where they ultimately transform into the concave-shaped red blood cells.