Critical shifts in lipid metabolism promote megakaryocyte differentiation and proplatelet formation
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Published:2023-08-31
Issue:9
Volume:2
Page:835-852
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ISSN:2731-0590
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Container-title:Nature Cardiovascular Research
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language:en
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Short-container-title:Nat Cardiovasc Res
Author:
de Jonckheere BiancaORCID, Kollotzek Ferdinand, Münzer PatrickORCID, Göb VanessaORCID, Fischer MelinaORCID, Mott Kristina, Coman Cristina, Troppmair Nina Nicole, Manke Mailin-ChristinORCID, Zdanyte Monika, Harm Tobias, Sigle ManuelORCID, Kopczynski Dominik, Bileck AndreaORCID, Gerner Christopher, Hoffmann Nils, Heinzmann David, Assinger AliceORCID, Gawaz MeinradORCID, Stegner DavidORCID, Schulze Harald, Borst OliverORCID, Ahrends RobertORCID
Abstract
AbstractDuring megakaryopoiesis, megakaryocytes (MKs) undergo cellular morphological changes with strong modification of membrane composition and lipid signaling. Here, we adopt a lipid-centric multiomics approach to create a quantitative map of the MK lipidome during maturation and proplatelet formation. Data reveal that MK differentiation is driven by an increased fatty acyl import and de novo lipid synthesis, resulting in an anionic membrane phenotype. Pharmacological perturbation of fatty acid import and phospholipid synthesis blocked membrane remodeling and directly reduced MK polyploidization and proplatelet formation, resulting in thrombocytopenia. The anionic lipid shift during megakaryopoiesis was paralleled by lipid-dependent relocalization of the scaffold protein CKIP-1 and recruitment of the kinase CK2α to the plasma membrane, which seems to be essential for sufficient platelet biogenesis. Overall, this study provides a framework to understand how the MK lipidome is altered during maturation and the effect of MK membrane lipid remodeling on MK kinase signaling involved in thrombopoiesis.
Funder
University of Vienna through seed funding Vienna doctoral school in Chemistry Deutsche Forschungsgemeinschaft
Publisher
Springer Science and Business Media LLC
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