How is Erythropoiesis Regulated

Erythropoietin is the hormone mainly involved in the regulation of formation of erythrocytes. Erythrocytes or red blood cells are incapable of dividing to replenish its number. However, the old erythrocytes have to be replaced by new cells. Hence, there is a mechanism by which new erythrocytes are produced; this mechanism is called erythropoiesis, and it occurs in the bone marrow. The main function of erythrocytes is the transportation of oxygen through the blood. Therefore, the number of circulating erythrocytes in the blood should be tightly regulated.

Key Areas Covered

1. What is Erythropoiesis
      – Definition, Stages
2. How is Erythropoiesis Regulated
     – Regulation through Erythropoietin and Other Factors

Key Terms: Bone Marrow, Erythropoiesis, Erythropoietin, Fibronectin, Gene Expression Regulation, Hemocytoblast 

What is Erythropoiesis

Erythropoiesis is the process by which erythrocytes are formed in the bone marrow. It occurs in the yolk sac during fetal development. In the third trimester in the fetal development, erythropoiesis occurs in the liver. After birth, it occurs in the bone marrow.

During erythropoiesis, mature red blood cells are formed from hematopoietic stem cells. Eight stages can be identified during the formation of fully-matured erythrocytes from a hemocytoblast. The first seven stages are taken place within the bone marrow. The final stage of development occurs in the bloodstream. The eight stages of erythropoiesis are described below.

1. Hemocytoblast – Hemocytoblast is the pluripotent hematopoietic stem cell.
2. Common myeloid progenitor – Hemocytoblast becomes the common myeloid progenitor, which is a multipotent stem cell.
3. Unipotent stem cell
4. Pronormoblast
5. Basophilic normoblast also called an erythroblast.
6. Polychromatophilic normoblast
7. Orthochromatic normoblast
8. Reticulocyte

Figure 1: Erythropoiesis

How is Erythropoiesis Regulated

The lifespan of erythrocytes is 120 days. Approximately 2×10¹¹ erythrocytes are produced in the body per day. Erythropoiesis is regulated by many factors.

1. Erythropoietin – The major factor that governs erythropoiesis is a hormone called erythropoietin. It is produced by the kidney. The main role of erythropoietin is to regulate differentiation, expansion, activation of erythroid-specific genes as well as apoptosis. 

Figure 2: Erythropoietin

2. Fibronectin – Fibronectin is an extracellular matrix protein that regulates proliferation of erythrocytes.
3. Gene expression – Other factors such as transcription factors, miRNA, post-translational modification of histones, cytokines, and cofactors are also involved in the regulation of erythropoiesis through the regulation of gene expression.

Conclusion

Erythropoiesis is the mechanism of formation of erythrocytes during the replenishing of new erythrocytes. It occurs in the bone marrow. The main factor involved in the regulation of erythrocytes is a hormone called erythropoietin. Some other factors are also involved in the regulation of gene expression to regulate erythropoiesis.

Reference:

1. Hattangadi, Shilpa M., et al. “From Stem Cell to Red Cell: Regulation of Erythropoiesis at Multiple Levels by Multiple Proteins, RNAs, and Chromatin Modifications.” Blood, American Society of Hematology, 8 Dec. 2011, Available here.