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3 results on '"Jonas Dehairs"'

1. Extracellular vesicle‐associated cholesterol supports the regenerative functions of macrophages in the brain

Author

Sam Vanherle, Jeroen Guns, Melanie Loix, Fleur Mingneau, Tess Dierckx, Flore Wouters, Koen Kuipers, Tim Vangansewinkel, Esther Wolfs, Paula Pincela Lins, Annelies Bronckaers, Ivo Lambrichts, Jonas Dehairs, Johannes V. Swinnen, Sanne G. S. Verberk, Mansour Haidar, Jerome J. A. Hendriks, and Jeroen F. J. Bogie

Subjects
cholesterol, extracellular vesicle, oligodendrocyte precursor cell differentiation, remyelination, repair‐associated macrophage, Cytology, QH573-671
Abstract

Abstract Macrophages play major roles in the pathophysiology of various neurological disorders, being involved in seemingly opposing processes such as lesion progression and resolution. Yet, the molecular mechanisms that drive their harmful and benign effector functions remain poorly understood. Here, we demonstrate that extracellular vesicles (EVs) secreted by repair‐associated macrophages (RAMs) enhance remyelination ex vivo and in vivo by promoting the differentiation of oligodendrocyte precursor cells (OPCs). Guided by lipidomic analysis and applying cholesterol depletion and enrichment strategies, we find that EVs released by RAMs show markedly elevated cholesterol levels and that cholesterol abundance controls their reparative impact on OPC maturation and remyelination. Mechanistically, EV‐associated cholesterol was found to promote OPC differentiation predominantly through direct membrane fusion. Collectively, our findings highlight that EVs are essential for cholesterol trafficking in the brain and that changes in cholesterol abundance support the reparative impact of EVs released by macrophages in the brain, potentially having broad implications for therapeutic strategies aimed at promoting repair in neurodegenerative disorders.

Published
2023
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2. Tracer Lipidomics

Author

Jonas Dehairs, Ine Koeken, Lake‐Ee Quek, Andrew Hoy, Bart Ghesquière, and Johannes V. Swinnen

Published
2023

3. Non‐small cell lung cancer is characterized by dramatic changes in phospholipid profiles

Author

Steffen Fieuws, Raf Van de Plas, Richard M. Caprioli, Muralidhararao Bagadi, Jonas Dehairs, Thomas Muley, Eyra Marien, Michael Thomas, Rita Derua, Jens Wouters, Michael Meister, Johannes V. Swinnen, Hendrik Dienemann, Sergio Bordel, Etienne Waelkens, Philipp A. Schnabel, and Jeffrey M. Spraggins

Subjects
Spectrometry, Mass, Electrospray Ionization, Cancer Research, Lung Neoplasms, education, Phospholipid, Biology, Phosphatidylinositols, Bioinformatics, Transcriptome, chemistry.chemical_compound, Tandem Mass Spectrometry, Carcinoma, Non-Small-Cell Lung, Lipidomics, medicine, Metabolome, Humans, Lung cancer, Phospholipids, health care economics and organizations, non-small cell lung cancer, phospholipids, mass spectrometry, lipidomics, 2D-imaging MS, Cancer, medicine.disease, Sphingomyelins, 3. Good health, Oncology, chemistry, Proteome, Cancer cell, Cancer research, Cancer Cell Biology
Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)-based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non-malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non-malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D-imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D-imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development. What's new? Cellular membranes are subject to extensive modification in cancer, often with marked alterations in phospholipid metabolism. The extent and nature of those changes are not fully known, however, particularly for non-small cell lung cancer (NSCLC). In this study, lipidomics analysis of phospholipid profiles uncovered dramatic differences between NSCLC and normal lung tissue. The differences were confirmed via 2D-imaging lipidomics in tissue sections. Lipid markers capable of discriminating between tumor and normal tissue and between different NSCLC subtypes were identified. The observed alterations in NSCLC phospholipid profiles may be biologically significant. Grant sponsor: EU FP7 (to J.Sw., M.M., T.M. and M.T.); Grant number: Canceralia EU-259737; Grant sponsor: Research Foundation-Flanders (FWO) (to J.Sw.); Grant number: G.0691.12; Grant sponsor: KU Leuven (to J.Sw.); Grant number: GOA/11/2009; Grant sponsor: Foundation Fournier Majoie (FFM) (to J.Sw.); Grant sponsor: Stichting tegen Kanker (to J.Sw.); Grant number: F/2014/324; Grant sponsor: Agency for Innovation by Science and Technology IWT-Flanders (to E.M. and J.D.; recipients of a fellowship); Grant sponsor: Olle Engkvist foundation (Sweden) (to S.B.); Grant sponsor: National Institutes of Health (to J.Sp., R.V. and R.M.C.); Grant numbers: NIH/NIGMS R01 GM058008-14 and NIH/NIGMS P41 GM103391-03

Published
2015

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