Mucin-type o-glycan in megakaryocyte differentiation

Abstract

To address the biological role of mucin-type O-glycans in hematopoietic cells, we conditionally ablated C1galt1, which is essential for synthesis of the core 1 structure of mucin-type O-glycans. Inducible, Mx1-cre-mediated C1galt1 conditional knockout (Mx1-C1) mice exhibited severe thrombocytopenia, giant platelets, and prolonged bleeding times. Mx1-C1 bone marrow contained a normal number of megakaryocytes and a normal DNA ploidy distribution in developing megakaryocytes. However, proplatelet-forming ability was markedly decreased in cultured Mx1-C1 primary megakaryocytes relative to that in primary wild-type megakaryocytes. Moreover, the expression of hypoglycosylated GPIbα protein in Mx1-C1 megakaryocytes and platelets was greatly reduced despite the fact that expression of GpIbα mRNA was unchanged. In this study, we showed that mucin-type O-glycans are essential for terminal megakaryocyte differentiation and platelet production. Loss of GPIbα O-glycosylation may affect its stability and susceptibility to protease.