The Serotonergic System in Hematopoiesis and Hematopoietic Disorders

Hematopoiesis is a complex process beginning with an uncommitted pluripotent hematopoietic stem cell capable to reconstitute the entire blood and immune systems. Despite extensive research, not all of the regulatory processes of hematopoietic stem cell proliferation and commitment are identified and fully understood. Monoamines including serotonin have been mainly investigated for their role as neurotransmitters or neuromodulators. However, deletion of the gene encoding the peripheral serotonin-synthesizing enzyme tryptophan hydroxylase-1 revealed multiple functions for components of the extra-neuronal system. In the following chapter, we will discuss the role of various components of peripheral serotonergic system, with a special emphasis on 5-HT2B receptors, as hematopoietic regulators for the activities of self-renewal, proliferation, differentiation, and mobilization of hematopoietic stem cells. Finally, we will relate these findings to human health issues. The serotonergic system, as a therapeutic target could have the capacity to regulate hematopoietic stem cells, making a curative cell therapy for blood cancers and diseases.