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Critical shifts in lipid metabolism promote megakaryocyte differentiation and proplatelet formation (Targeted lipidomics assay 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.

Targeted lipidomics assay without inhibition are reported in the current assay MTBLS6084

Shotgun lipidomics assays without inhibition are reported in MTBLS6082

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

INSTRUMENT(S): Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Nils Hoffmann

PROVIDER: MTBLS6084 | MetaboLights | 2023-07-26

REPOSITORIES: MetaboLights

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			Action	DRS
	MTBLS6084	Other
	FILES	Other
	a_MTBLS6084_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	files-all.json	Other
	i_Investigation.txt	Txt

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

Project description: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 MTBLS6082Shotgun lipidomics assays after inhibition with FSG67 and Triacsin C are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6083' rel='noopener noreferrer' target='_blank'>MTBLS6083</a>Targeted lipidomics assay without inhibition are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6084' rel='noopener noreferrer' target='_blank'>MTBLS6084</a>

2023-07-26 | MTBLS6082 | MetaboLights

Critical shifts in lipid metabolism promote megakaryocyte differentiation and proplatelet formation (Shotgun lipidomics assays after inhibition with FSG67 and Triacsin C)

Project description: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 after inhibition with FSG67 and Triacsin C are reported in the current assay MTBLS6083Shotgun lipidomics assays without inhibition are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6082' rel='noopener noreferrer' target='_blank'>MTBLS6082</a>Targeted lipidomics assay without inhibition are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6084' rel='noopener noreferrer' target='_blank'>MTBLS6084</a>

2023-07-26 | MTBLS6083 | MetaboLights

Increased lipid transport and de novo synthesis lead to dynamic lipidome remodeling and regulation of lipid-dependent kinases during megakaryopoiesis and proplatelet formation

Project description:During megakaryopoiesis and consecutive platelet production, megakaryocytes undergo robust cellular morphological changes which are associated with the reprogramming of signaling pathways. Moreover, it can be assumed that lipid membrane composition and signaling are strongly modified. However, the knowledge of lipid alteration during megakaryopoiesis and which pathways are involved is still lacking. Here, we use a lipid-centric multiomics approach to create a quantitative map of the megakaryocyte lipidome during maturation and proplatelet formation. Our data reveal that megakaryocyte differentiation is driven by an increased fatty acyl import and de novo lipid synthesis, resulting in the modulation towards an anionic membrane phenotype. This phenotype and the upregulation of diacylglycerols highly correlate with the activation of lipid-dependent kinases such as PKC and BTK. Using inhibitors of fatty acid import and phospholipid synthesis proved to block membrane remodeling and kinase activation and directly reduced proplatelet formation. Altogether, this study provides a framework for understanding how membrane lipid remodeling during megakaryocyte differentiation impacts kinase signaling and proplatelet formation while providing a knowledge base to exploit megakaryopoiesis.

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