Project description:Characterization of the lysine β-hydroxybutyrylome, proteome-wide, will start to define its cellular targets and enable investigation of its impact under ketogenesis. Here, we show the induction of global protein Kbhb in the liver. We identified 891 sites of Kbhb within 267 proteins belonging to macronutrient, detoxification and 1-carbon metabolic pathways, among others, in starved liver.
Project description:Proteomics of pure cell populations provides a powerful approach to globally investigate biological function of individual cell types in mammalian organs. Here, we applied latest mass spectrometry techniques for in-depth proteomic analysis of freshly isolated hepatic cell types (HC-types) from murine liver. This study provides a valuable comprehensive resource for liver biology and biomedicine.
Project description:In this study RNAseq was used for studying the transcriptome profile of primary liver sinusoidal endothelial cells (LSECs) isolated from non-lesioned non-tumorous liver tissues (considered as healthy) and from cirrhotic liver explants (ethanol etiology). Results showed different transcriptomic profile between two populations of LSECs with 1374 significant deregulated genes (fold-change>1.5 and p-vale<0.05) in cirrhotic-LSECs compared with healthy-LSECs.
Project description:Abstract The liver is the largest solid organ and a primary metabolic hub. In recent years, intact cell nuclei were used to perform single-nuclei RNA-seq (snRNA-seq) for tissues difficult to dissociate and for flash-frozen archived tissue samples to discover unknown and rare cell sub-populations. In this study, we performed snRNA-seq of a liver sample to identify sub-populations of cells based on nuclear transcriptomics. In 4,282 single nuclei we detected on average 1,377 active genes and we identified seven major cell types. We integrated data from 94,286 distal interactions (p<0.05) for 7,682 promoters from a targeted chromosome conformation capture technique (HiCap) and mass spectrometry (MS) proteomics for the same liver sample. We observed a reasonable correlation between proteomics and in silico bulk snRNA-seq (r=0.47) using tissue-independent gene-specific protein abundancy estimation factors. We specifically looked at genes of medical importance. The DPYD gene is involved in the pharmacogenetics of fluoropyrimidines toxicity and some of its variants are analyzed for clinical purposes. We identified a new putative polymorphic regulatory element, which may contribute to variation in toxicity. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and we investigated all known risk genes. We identified a complex regulatory landscape for the SLC2A2 gene with 16 candidate enhancers. Three of them harbor somatic motif breaking and other mutations in HCC in the Pan Cancer Analysis of Whole Genomes dataset and are candidates to contribute to malignancy. Our results highlight the potential of a multi-omics approach in the study of human diseases.
Project description:Proteomics of pure cell populations provides a powerful approach to globally investigate biological function of individual cell types in mammalian organs. Here, we applied latest mass spectrometry techniques for in-depth proteomic analysis of freshly isolated hepatic cell types (HC-types) from murine liver. This study provides a valuable comprehensive resource for liver biology and biomedicine.
Project description:Liver disease alters the gut microenvironment by liver-gut axis. To investigate the composition and transcriptome changes of various intestinal cell populations in liver cirrhosis, we delineated a single-cell atlas of the colon from mice treated CCl4 for 6 weeks.
