MetaboLights

application/xml

ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14790/m_MTBLS14790_LCMS_reverse-phase_POS_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14790/m_MTBLS14790_LCMS_reverse-phase_NEG_v2_maf.tsvftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14790/i_Investigation.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14790/s_MTBLS14790.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14790/a_MTBLS14790_LC-MS_negative_reverse-phase.txtftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14790/a_MTBLS14790_LC-MS_positive_reverse-phase.txtprimaryOK200ftp://ftp.ebi.ac.uk/pub/databases/metabolights/studies/public/MTBLS14790Raw MS data were processed using LipidSearch (v4.1, Thermo Fisher Scientific) for lipid identification and quantification. Peak extraction and lipid matching were performed using Product Search mode with the following parameters: parent and fragment ion mass tolerance of 5 ppm, relative fragment ion response threshold of 5.0%, peak alignment mass tolerance of 5 ppm, M-score ≥ 5.0, C-score ≥ 2.0, and retention time tolerance of 0.1 min. Identification grades A, B, C, and D were accepted. Positive ion mode adducts included [M+H]+, [M+NH4]+, and [M+Na]+; negative ion mode adducts included [M−H]-, [M−2H]2-, and [M+HCOO]-.MetaboLightsPublicLiquid Chromatography MS - negative - reverse-phaseLiquid Chromatography MS - positive - reverse-phaseChromatographic separation was performed on a CSH C18 column (1.7 μm, 2.1 × 100 mm, Waters) at 55°C with a flow rate of 0.4 mL/min and an injection volume of 5 μL. Mobile phase A and B for positive ion mode consisted of acetonitrile/water (60:40, v/v) with 10 mM ammonium formate and 0.1% formic acid, and isopropanol/acetonitrile (90:10, v/v) with 10 mM ammonium formate and 0.1% formic acid, respectively. For negative ion mode, mobile phase A and B were acetonitrile/water (60:40, v/v) and isopropanol/acetonitrile (90:10, v/v), both containing 10 mM ammonium formate. Gradient elution was applied as follows: 0–0.1 min, 40% B; 0.1–7 min, 40–99% B; 7–8 min, 40% B.Brain corticogenesis promotes SARS-CoV-2 neuro-glial tropism through lipid-dependent viral replication.Nhu MaiYeungnam UniversityhIPSC-derived CBOmass spectrometry assayUp to 25 mg of each sample was suspended in 800 μL of pre-chilled dichloromethane/methanol (3:1, v/v) containing 10 μL of an internal standard cocktail, with two steel beads added for homogenization. Samples were homogenized using a TissueLyser (5 min), sonicated on ice (10 min), and incubated overnight at −20°C. Following centrifugation (25,000 × g, 4°C, 15 min), 600 μL of the supernatant was collected and dried under vacuum. The dried residue was reconstituted in 120 μL of isopropanol/acetonitrile/water (2:1:1, v/v/v), shaken for 10 min, and sonicated on ice for 10 min. Samples were centrifuged again (25,000 × g, 4°C, 15 min), and 20 μL from each sample was pooled to prepare a QC sample. The remaining supernatant was subjected to UPLC-MS analysis.Homo sapienshttps://www.ebi.ac.uk/metabolights/MTBLS14790Nhu Mai. Yeungnam University. 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. ntqmai@yu.ac.kr.Da-Jin Jeong. Yeungnam University. 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea.Byoung-San Moon. Yeungnam University. 280 Daehak-Ro, Gyeongsan, Gyeongbuk 38541, Republic of Korea. bsmoon@yu.ac.kr.The off-line data of mass spectrometry was imported to Lipidsearch v.4.1 (Thermo Fisher Scientific, USA) software for data analysis.Developmental stagentqmai@yu.ac.krUninfected EB60 and EB120 were collected, washed with PBS, decanted, and stored at -80oC until extraction.MetabolomicscorticogenesishIPSCLipid remodelinguntargeted analysisWaters ACQUITY UPLC I-Class SystemHomo sapiensLipidomicsOrbitrap Exploris 480untargeted metabolite profilingexperimental sampleBrain maturationlipidomicgliogenesisCerebral Organoidcerebral cortex developmenthIPSC-derived CBOcorticogenesishIPSCLipid remodelinguntargeted analysisWaters ACQUITY UPLC I-Class SystemHomo sapiensLipidomicsOrbitrap Exploris 480untargeted metabolite profilingexperimental sampleBrain maturationlipidomicgliogenesisCerebral Organoidcerebral cortex developmenthIPSC-derived CBOMass spectrometry data were acquired using an Orbitrap Exploris 480 mass spectrometer (Thermo Fisher Scientific) operated in data-dependent acquisition (DDA) mode. Full scan MS1 spectra were collected over a mass range of m/z 200–2000 at a resolution of 120,000, with a normalized AGC target of 300% and a maximum injection time of 100 ms. The top 9 precursor ions were selected for fragmentation (MS2) at a resolution of 30,000, with a normalized AGC target of 100%, automatic maximum injection time, and stepped collision energies of 15, 30, and 45 eV (NCE). Electrospray ionization (ESI) was performed with a sheath gas flow rate of 40 arbitrary units, auxiliary gas flow rate of 10 arbitrary units, and ion transfer tube temperature of 320°C. The auxiliary gas heating temperature was set to 350°C. Spray voltage was 3.80 kV in positive ion mode and 3.20 kV in negative ion mode.falseBrain corticogenesis promotes SARS-CoV-2 neuro-glial tropism through lipid-dependent viral replicationWhile extensive research has examined the neuroinvasiveness of SARS-CoV-2, its relationship with brain maturation remains unclear. Using a multi-omics approach, we established cerebral organoids (CBOs) at day 60 (EB60) and day 120 (EB120) to model immature and mature developmental stages. We found that enhanced corticogenesis and gliogenesis during maturation are associated with substantial alterations in lipid metabolism, functionally linking these processes to coordinated molecular and functional brain development. To directly characterize the lipid landscape accompanying brain maturation, we performed untargeted lipidomics on healthy EB60 and EB120 organoids, revealing a broad remodeling of the lipid metabolome in mature CBOs and providing a quantitative basis for the observed metabolic shift. Leveraging this model, we provide the first quantitative insights into long-term viral propagation kinetics up to 20 days post-infection, revealing significantly higher infectivity in mature CBOs. Single-cell transcriptomics, RT-qPCR and immunohistochemistry revealed upregulation of lipid-associated genes in EB120, suggesting a key driver of increased susceptibility. Consistently, pharmacological lipid reduction attenuated SARS-CoV-2 infection. Our findings establish a mechanistic link between intrinsic brain maturation and viral susceptibility mediated by lipid remodeling, supported by lipidomic profiling of healthy organoids, and suggest lipid-lowering strategies as potential candidates for therapeutic repurposing in COVID-19.2026-06-182026-06-18MTBLS14790