Critical shifts in lipid metabolism promote megakaryocyte differentiation and proplatelet formation

Bianca de Jonckheere, Ferdinand Kollotzek, Patrick Münzer, Vanessa Göb, Melina Fischer, Kristina Mott, Cristina Coman, Nina Nicole Troppmair, Mailin Christin Manke, Monika Zdanyte, Tobias Harm, Manuel Sigle, Dominik Kopczynski, Andrea Bileck, Christopher Gerner, Nils Hoffmann, David Heinzmann, Alice Assinger, Meinrad Gawaz, David StegnerHarald Schulze, Oliver Borst (Korresp. Autor*in), Robert Ahrends (Korresp. Autor*in)

Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed

Abstract

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.

OriginalspracheEnglisch
Seiten (von - bis)835-852
Seitenumfang18
FachzeitschriftNature Cardiovascular Research
Jahrgang2
Ausgabenummer9
DOIs
PublikationsstatusVeröffentlicht - Sep. 2023

ÖFOS 2012

  • 301302 Lipidforschung
  • 301114 Zellbiologie
  • 301303 Medizinische Biochemie
  • 302032 Kardiologie

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