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O‐GlcNAcylation Regulates Megakaryopoiesis and Thrombopoiesis

A new STEM CELLS study from researchers led by Sudjit Luanpitpong (Mahidol University, Bangkok, Thailand) reveals that cellular O‐GlcNAcylation levels decline along the course of megakaryocyte differentiation from human‐derived hematopoietic stem and progenitor cells (HSPCs). Under normal conditions, O‐GlcNAcylation stabilizes c‐Myc by interfering with ubiquitin‐mediated proteasomal degradation. Inhibition of O‐GlcNAc transferase (OGT) disrupts the O‐GlcNAcylation of c‐Myc to prompt c‐Myc degradation, integrin perturbation, and platelet production. Therefore, inhibition of OGT and O‐GlcNAcylation via small-molecule inhibition or genetic manipulation may hold promise for future clinical applications to improve megakaryocyte differentiation and platelet production.