Erythropoiesis is the process of erythrocyte development
Erythrocyte (aka, red blood cell) formation occurs primarily in the red marrow of
spongy bone, in close association with macrophages.
Pluripotent hematopoieticstem cell (HSC)
Pluripotent means it has the potential to form any blood cell type. Under stimulation from PU.1 transcription factor, gives rise to the common myeloid progenitor (CMU)
CMU
Also called the "CFU-GEMM," because it can give rise to any of the following lineages: Granulocytes, Erythrocytes, Monocytes, and Megakaryocytes
CFU-MegE (Colony Forming Units – Megakaryocytes and Erythrocytes)
Blast-Forming Units – Erythrocytes (BFU-E)
BFU-E requires the following for proper development: Stem Cell Factors, Interleukins 3 and 6, and IGF-1.
BFU-E cells give rise to Colony-Forming Units – Erythrocytes (CFU-E).
CFU-E
By default, the fate of the CFU-E is apoptosis
EPO - Hormone produced by the kidneys, blocks CFU-E cell death that allows initiation of the erythroid series
The differentiation and maturation of erythroblasts, aka, normoblasts; this process appears to require an intimate relationship with the macrophage, which forms the basis of the macrophage-erythroid island.
Requires:
Fibronectin, which is an extracellular glycoprotein synthesized by fibroblasts, and other adhesion molecules that secure the macrophage-erythroblast island.
KLF-1 (Kruppel-Like Factor) transcription factor is necessary for the production of adult hemoglobin; abnormally low levels are associated with higher levels of fetal hemoglobin (Hereditary Persistence of Fetal Hemoglobin). (incidentally, this transcription factor has been suggested to play additional essential roles in erythropoiesis).
Erythrocyte maturation factors, including Vitamin B12 and folic acid, are necessary for healthy red blood cell development; deficiencies produce malformed cells and, consequently, anemias.
Proerythroblast: The first stage in the erythroid series, comprises a relatively large basophilic cell inhabited by a large nucleus; we've labeled the fine, granular nuclear chromatin.
Basophilic erythroblast: Hemoglobin synthesis is indicated by condensation of the nuclear chromatin.
Polychromatophilic erythroblast: Increasing presence of hemoglobin renders the cell both basophilic and acidophilic — hence, "poly" chromatophilic.
Polychromatophilic erythroblastis the last stage in which cell division via mitosis is possible (intertextual variation on this timing exists).
Orthochromatic (aka, acidophilic) erythroblast: The abundant hemoglobin renders the cytoplasm acidophilic.
As the chromatin degenerates, it leaves a dense, basophilic mass in the pyknotic nucleus (pyknotic = nucleus undergoing necrosis).
Reticulocyte: Nucleus is extruded from the orthochromatic erythroblast as it transitions to a reticulocyte; is engulfed by the macrophage and phagocytosed.
Other organelles, including the mitochondria, suffer the same fate; recognize that this has functional consequences for the mature red blood cell - without mitochondria, they rely on anaerobic respiration – and, thus, consume none of the oxygen as they transport it to body tissues.
Some organelle remnants, particularly of the endoplasmic reticulum, may still be visible in the reticulocyte; However, these, too, will be extruded and phagocytosed by the macrophage.
Reticulocyte exits the red marrow via the medullar venous sinus, travels in the bloodstream to the spleen for the final stages of maturation.
Erythrocyte: Emerges from the spleen to perform its gas transport duties in the circulatory system.
The lifespan of the average erythrocyte is 120 days; After this period, defects in the cell membrane render it susceptible to rupture or
phagocytosis by splenic macrophages.
