Project description:We studied the lipidome (236 individual lipid species including sphingolipids, ceramides, cholesterol, gangliosides, phosphatidylethanolamines) in basal and LPS-stimulated human monocyte derived macrophages (MDMs) over a time-course by LC-MS (30min, 3h, 8h, 16h; n=12 human donors). In order to explore how transcriptomic changes induced by LPS stimulation can correlate with changes in the lipidome, we performed RNAsequencing on MDMs from 4 donors over a time-course (30min, 3h, 8h, 16h)
Project description:We used a comprehensive approach that combined proteome, lipidome, and metabolome data to investigate the segmentation atlas of hepatocellular carcinoma (HCC).
Project description:We provide an atlas of gene and protein expression in Arabidopsis root hair cells, generated by paired-end RNA-seq and LC/MS-MS analysis from protoplasts that carry the root hair-specific pEXP7-GFP reporter construct. In total, transcripts from 23,234 genes were detected in root hairs; those related to cell wall biosynthesis and translation differed most dramatically in abundance when compared to non-GFP root protoplasts.
Project description:Compartmentalized inflammation is considered a critical factor in driving the progression of multiple sclerosis (MS). Yet, the mechanisms sustaining its persistence remain poorly understood. A hallmark of this persistent and slowly evolving inflammatory process are chronic active MS lesions. In this study, we created a high-resolution, single-cell molecular and spatial atlas of chronic inflammation in MS. To accomplish this, we combined single-nucleus RNA sequencing (snRNA-seq) with single-cell spatial transcriptomics using multiplexed error-robust fluorescence in situ hybridization (MERFISH) to examine MS lesions, specifically focusing on those exhibiting chronic active immune pathology characterized by lymphocyte presence. Our integrative profiling uncovered the molecular landscape of glial and immune cells, their disease-associated states, and the surrounding microenvironments. Within the lesion rim, we identified CD8+ T cell niches with lipid-associated microglia. To demonstrate the utility of this spatially resolved atlas of chronic active MS lesions as a resource for future discovery, we investigated the role of lipid-associated microglia in experimental autoimmune encephalomyelitis (EAE). Our findings showed that inhibiting cholesterol efflux increased the formation of lipid-storing phagocytes, "foamy microglia," which actively drive inflammatory processes in EAE and represent tractable therapeutic targets for pharmacological modulators of sterol metabolism. These results provide a framework for system-level insights into cell-type diversity and represent a valuable resource for advancing the study of neuroinflammation in MS.
Project description:The physiological role of ubiquitous rhomboid proteases, membrane-integral proteins that cleave their substrates inside the lipid bilayer, is ill-defined in prokaryotes. The two rhomboid genes cg0049 and cg2767 of Corynebacterium glutamicum were deleted and consequences investigated in respect to growth phenotype, stress resistance, transcriptome, proteome and lipidome composition.
Project description:We used state of the art mass spectrometry (MS) and RNA sequencing (RNA-Seq) to provide the first integrated proteomic, phosphoproteomic and transcriptomic atlas of the animal model Mus musculu . We measured 66 murine pancreatic ductal adenocarcinoma cell lines (66 proteomes and 66 phosphoproteome) and 41 healthy tissues (41 proteomes, 41 phosphoproteome, and 29 transcriptomes). The employed MS-based and bioinformatics strategy identified >17,000 proteins and >50,000 phosphorylation sites, providing expression evidence for ~76% of the 22,437 protein-coding genes reported in UniProtKB. The RNA-Seq strategy resulted in the quantification of 21,261 unique gene that were expressed in at least one of the 29 sequenced tissue.
Project description:Multiple sclerosis (MS) is a debilitating demyelinating disease characterized by remyelination failure attributed to inadequate oligodendrocyte precursor cells (OPCs) differentiation and aberrant astrogliosis. A comprehensive cell atlas reanalysis of clinical specimens brings to light heightened clusterin (CLU) expression in a specific astrocyte subtype links to active lesions in MS patients. Our investigation reveals elevated astrocytic CLU levels in both active lesions of patient tissues and female murine MS models. CLU administration stimulates primary astrocyte proliferation while concurrently impedes astrocyte-mediated clearance of myelin debris. Intriguingly, CLU overload directly impedes OPCs differentiation and induces OPCs and OLs apoptosis. Mechanistically, CLU suppresses PI3K-AKT signaling in primary OPCs via very low-density lipoprotein receptor. Pharmacological activation of AKT rescues the damage inflicted by excess CLU on OPCs and ameliorates demyelination in the corpus callosum. Furthermore, conditional knockout of CLU emerges as a promising intervention, showcasing improved remyelination processes and reduced severity in murine MS models.
Project description:We generated a paired snRNA-seq (n= 15) and spatial transcriptomics (n=19) dataset from subcortical chronic active and chronic inactive MS lesions, identifying spatial niches and key cell interactions driving inflammation and disease progression at the lesion rim. This repository offers access to all the trancriptomics data that was used in the paper. It includes, all FASTQ files for both transcriptomics, along with the necessary files for running spatial transcriptomic samples (H&E images and JSON files), as well as the curated atlas, all derived cell subtype atlases from the main atlas and all curated ST slides.