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The red blood cells in the human body have a lifespan of about 130 days. Therefore, our body has a system to regulate the number of each type of blood cell in the bloodstream and produces more than 500 billion blood cells every day. This process is called hematopoiesis. In vertebrates, most hematopoiesis takes place in the bone marrow and is regulated by a limited number of hematopoietic stem cells (HSC, or blood stem cells).
Hematopoietic stem cells are multipotent and have the ability to self-renew. They are able to differentiate into all blood lineages, thereby permanently maintaining the adult hematopoietic system throughout the life span of an individual.
The process of hematopoiesis is highly conserved in vertebrates and proceeds in two distinct waves. In the zebrafish embryo, the first, primitive wave generates a mesodermal cell type that differentiates into hematopoietic cells and endothelial cells in the intermediate cell mass (ICM). The resulting cells are transient, non-pluripotent, and lack (self-)renewal capacity.
In the second, definitive wave, endothelial cells in the dorsal aorta (DA; or aorta-gonad-mesonephros region (AGM)) differentiate into multipotent hematopoietic stem cells (HSC; or also called hematopoietic stem cells). This process, is called endothelial to hemogenic transition (EHT), into multipotent hematopoietic stem cells (HSC; or also termed hematopoietic stem cells). Subsequently, these HSCs migrate to their first stem cell niche, the caudal hematopoietic tissue (CHT), to proliferate and eventually populate the lymphopoietic and hematopoietic organs, thymus and kidney. HSCs generated during the definitive wave have the potential to generate all the blood cells of the adult organism for life. Hematopoietic stem cell transplants are used in the clinic for the treatment of cancers and other immune system disorders.