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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

PROVIDER: MTBLS6082 | MetaboLights | 2023-07-26

REPOSITORIES: MetaboLights

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			Action	DRS
	Blank_01.mzML	Mzml
	Blank_01.raw	Raw
	Blank_02.mzML	Mzml
	Blank_02.raw	Raw
	Blank_03.mzML	Mzml

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Similar Datasets

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

Critical shifts in lipid metabolism promote megakaryocyte differentiation and proplatelet formation (Targeted lipidomics assay 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. Targeted lipidomics assay without inhibition are reported in the current assay MTBLS6084Shotgun lipidomics assays without inhibition are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS6082' rel='noopener noreferrer' target='_blank'>MTBLS6082</a>Shotgun 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>

2023-07-26 | MTBLS6084 | 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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Energy metabolism disorders during in vitro maturation affect bovine blastocysts transcriptome, lipidome, and metabolome

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2023-05-31 | GSE218045 | GEO

Spatial lipidomic profiling of mouse joint tissue demonstrates the essential role of PHOSPHO1 in growth plate homeostasis

Project description:Lipids play a crucial role in signalling and metabolism, regulating the development and maintenance of the skeleton. Membrane lipids have been hypothesised to act as intermediates upstream of orphan phosphatase 1 (PHOSPHO1), a major contributor to phosphate generation required for bone mineralisation. Here, we spatially resolve the lipid atlas of the healthy mouse knee and demonstrate the effects of PHOSPHO1 ablation on the growth plate lipidome. Lipids spanning 17 subclasses were mapped across the knee joints of healthy juvenile and adult mice using matrix-assisted laser desorption ionisation imaging mass spectrometry (MALDI-IMS), with annotation supported by shotgun lipidomics. Multivariate analysis identified 96 and 80 lipid ions with differential abundances across joint tissues in juvenile and adult mice respectively. In both ages, marrow was enriched in phospholipid platelet activating factors (PAFs) and related metabolites, cortical bone had a low lipid content, while lysophospholipids were strikingly enriched in the growth plate, an active site of mineralisation and PHOSPHO1 activity. Spatially-resolved profiling of PHOSPHO1-knockout (KO) mice across the resting, proliferating, and hypertrophic growth plate zones revealed 272, 306, and 296 significantly upregulated, and 155, 220 and 190 significantly downregulated features, respectively, relative to wild type (WT) controls. Of note, phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, lysophosphatidylethanolamine and phosphatidylethanolamine derived lipid ions were upregulated in PHOSPHO1-KO versus WT. Our imaging pipeline has established a spatially-resolved lipid signature of joint tissues and has demonstrated that PHOSPHO1 ablation significantly alters the growth plate lipidome, highlighting an essential role of the PHOSPHO1-mediated membrane phospholipid metabolism in lipid and bone homeostasis.

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ATGL deletion in castration-resistant prostate cancer cell line

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