Regulation of the genetic code in megakaryocytes and platelets

Abstract

Platelets are generated from nucleated precursors referred to as megakaryocytes. The formation of platelets is one of the most elegant and unique developmental processes in eukaryotes. Because they enter the circulation without nuclei, platelets are often considered simple, non-complex cells that have limited functions beyond halting blood flow. However, emerging evidence over the past decade demonstrates that platelets are more sophisticated than previously considered. Platelets carry a rich repertoire of messenger RNAs (mRNAs), microRNAs (miRNAs), and proteins that contribute to primary (adhesion, aggregation, secretion) and alternative (immune regulation, RNA transfer, translation) functions. It is also becoming increasingly clear that the 'genetic code' of platelets changes with race, genetic disorders, or disease. Changes in the 'genetic code' can occur at multiple points including megakaryocyte development, platelet formation, or in circulating platelets. This review focuses on regulation of the 'genetic code' in megakaryocytes and platelets and its potential contribution to health and disease.

Keywords: genes; human; megakaryocytes; platelets; thrombopoiesis.

Figure 1. Megakaryocyte Investment of the Genetic Code into Platelets

Variations in race, genetic mutations, or acute disease are associated with changes in the genetic code (i.e., mRNA and miRNA expression patterns) in megakaryocytes. Changes in the megakaryocyte genetic code are then transferred into developing platelets that are released into the circulation. Alterations in the platelet transcriptome and corresponding proteins influence functional responses in both health and disease.