TY - JOUR
T1 - Critical shifts in lipid metabolism promote megakaryocyte differentiation and proplatelet formation
AU - de Jonckheere, Bianca
AU - Kollotzek, Ferdinand
AU - Münzer, Patrick
AU - Göb, Vanessa
AU - Fischer, Melina
AU - Mott, Kristina
AU - Coman, Cristina
AU - Troppmair, Nina Nicole
AU - Manke, Mailin Christin
AU - Zdanyte, Monika
AU - Harm, Tobias
AU - Sigle, Manuel
AU - Kopczynski, Dominik
AU - Bileck, Andrea
AU - Gerner, Christopher
AU - Hoffmann, Nils
AU - Heinzmann, David
AU - Assinger, Alice
AU - Gawaz, Meinrad
AU - Stegner, David
AU - Schulze, Harald
AU - Borst, Oliver
AU - Ahrends, Robert
N1 - Accession Number: WOS:001127053400002
PubMed ID: 38075556
PY - 2023/9
Y1 - 2023/9
N2 - During 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.
AB - During 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.
UR - http://www.scopus.com/inward/record.url?scp=85169308184&partnerID=8YFLogxK
U2 - 10.1038/s44161-023-00325-8
DO - 10.1038/s44161-023-00325-8
M3 - Article
AN - SCOPUS:85169308184
SN - 2731-0590
VL - 2
SP - 835
EP - 852
JO - Nature Cardiovascular Research
JF - Nature Cardiovascular Research
IS - 9
ER -