Critical shifts in lipid metabolism promote megakaryocyte differentiation and proplatelet formation (Shotgun lipidomics assays without inhibition)

ABSTRACT:

During megakaryopoiesis, megakaryocytes (MK) undergo cellular morphological changes with strong modification of membrane composition and lipid signaling. Here we adopt a lipid-centric multi-omics 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 impact of MK membrane lipid remodeling on MK kinase signaling involved in thrombopoiesis.

Shotgun lipidomics assays without inhibition are reported in the current study MTBLS6082

Shotgun lipidomics assays after inhibition with FSG67 and Triacsin C are reported in MTBLS6083

Targeted lipidomics assay without inhibition are reported in MTBLS6084

INSTRUMENT(S): Direct infusion MS - positive, Direct infusion MS - negative

SUBMITTER: Nils Hoffmann 

PROVIDER: MTBLS6082 | MetaboLights | 2023-07-26

REPOSITORIES: MetaboLights