Mass-Guided Single-Cell MALDI Imaging of Low-Mass Metabolites Reveals Cellular Activation Markers.

Single-cell MALDI mass spectrometry imaging (MSI) of lipids and metabolites >200 Da has recently come to the forefront of biomedical research and chemical biology. However, cell-targeting and metabolome-preserving methods for analysis of low mass, hydrophilic metabolites (<200 Da) in large cell populations are lacking. Here, the PRISM-MS (PRescan Imaging for Small Molecule - Mass Spectrometry) mass-guided MSI workflow is presented, which enables space-efficient single cell lipid and metabolite analysis.

Integrated metabolic-transcriptomic network identifies immunometabolic modulations in human macrophages.

Macrophages exhibit diverse phenotypes and respond flexibly to environmental cues through metabolic remodeling. In this study, we present a comprehensive multi-omics dataset integrating intra- and extracellular metabolomes with transcriptomic data to investigate the metabolic impact on human macrophage function. Our analysis establishes a metabolite-gene correlation network that characterizes macrophage activation.

Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation.

Unlabelled: An in-depth multiomic molecular characterization of PARP inhibitors revealed a distinct poly-pharmacology of niraparib (Zejula) mediated by its interaction with lanosterol synthase (LSS), which is not observed with other PARP inhibitors. Niraparib, in a similar way to the LSS inhibitor Ro-48-8071, induced activation of the 24,25-epoxysterol shunt pathway, which is a regulatory signaling branch of the cholesterol biosynthesis pathway. Interestingly, the combination of an LSS inhibitor with a PARP inhibitor that does not bind to LSS, such as olaparib, had an additive effect on killing cancer cells to levels comparable with niraparib as a single agent.

Consistency across multi-omics layers in a drug-perturbed gut microbial community.

Multi-omics analyses are used in microbiome studies to understand molecular changes in microbial communities exposed to different conditions. However, it is not always clear how much each omics data type contributes to our understanding and whether they are concordant with each other. Here, we map the molecular response of a synthetic community of 32 human gut bacteria to three non-antibiotic drugs by using five omics layers (16S rRNA gene profiling, metagenomics, metatranscriptomics, metaproteomics and metabolomics).

Metabolic rewiring revealed by cell-specific rate analyses from nontargeted exometabolomics during simultaneous consumption of glucose and lactic acid in a CHO fed-batch process.

Previously, we reported, based on an untargeted metabolomics, carnitine derivatives are part of a mechanism to overcome impaired mitochondrial functioning triggered by an acyl-group overflow in CHO cells. In this study, we analyzed the cell-specific rates of 24 selected metabolites using two metrics: correlation coefficients and root-mean-square deviations (RMSDs) between glucose-fed versus glucose/lactic acid-fed cultures. The time-course profiles of acetylcarnitine, adipoylcarnitine, glutarylcarnitine, glutamate, and succinate exhibited significant negative correlations between the two culture conditions.