Liver single-cell RNA sequencing reveals the transcriptomic landscape and gene regulation of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver
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ABSTRACT:
PROVIDER: PRJNA701070 | ENA |
REPOSITORIES: ENA
Dataset's files
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| SRR13673857.fastq.gz | Fastqsanger.gz |
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2020-07-30 | GSE135951 | GEO
Project description:The human liver functions through a complex interplay of parenchymal and non-parenchymal cells, which participate in performing many essential aspects of metabolism and secretion. Mass spectrometry-based proteomic analysis of intact tissue has improved the understanding of these processes, by providing an in-depth view of the human liver proteome. However, the predominance of parenchymal cells, i.e. hepatocytes, means that the total tissue proteome mainly reflects hepatocyte expression. In this study, we therefore used quantitative label-free proteomic analysis to analyze the proteomes of the major parenchymal and non-parenchymal cell types in the human liver, i.e. hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells. We found that our data recapitulated specific functional differences between cell types, meaning that it can be used to reliably probe various aspects of cellular interplay. Thus, the data we provide constitutes a unique resource for exploring the human liver proteome at major cell type resolution.
2020-04-09 | PXD012615 | Pride
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2013-05-01 | E-GEOD-45206 | biostudies-arrayexpress
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2024-04-04 | GSE202379 | GEO
Project description:Objective：Phospholipase D1 (PLD1), a phosphatidylcholine-hydrolyzing enzyme, has been found to be involved in cellular lipid metabolism. However, how PLD1 involves in hepatocyte lipid metabolism and thus affects non-alcoholic fatty liver diseases (NAFLD) has not been explicitly explored. Method: NAFLD is induced in hepatocyte-specific Pld1 knockout (Pld1(H)-KO) mice or control (Pld1-Flox) mice with a high fat diet (HFD) for 20 weeks. Plasma glucose and lipid levels, liver lipid and function parameters and inflammation- and fibrogenesis-related gene expression levels were studied. Changes in lipid composition of liver were detected by lipidomic analyses. Changes in gene expression profile were detected by mRNA sequencing. In vitro, alpha mouse liver 12 (AML12) cells were incubated with sodium palmitate (SP) to explore the mechanisms of PLD1 on development of NAFLD. The protein levels of PLD1 and CD36 were detected in the liver tissues of NAFLD patients. Finally, the therapeutic effect of NAFLD by inhibiting PLD with 5-Fluoro-2-indolyl deschlorohalopemide (FIPI) was examined. Results: PLD1 expression levels were increased in the liver tissues of NAFLD patients and the hepatocytes of HFD-induced mice. Compared with Pld1-Flox mice, Pld1(H)-KO mice exhibited lower plasma glucose and lipids levels, and decreased lipid accumulation, inflammation and fibrosis related gene expression levels in the liver tissues after HFD feeding. Inhibition of hepatocyte PLD1 significantly altered lipid composition, especially phosphatidic acids (PA) and lyso-PAs (LPA) levels in the liver tissues after NAFLD. Transcriptomic analysis showed that hepatocyte specific deficiency of PLD1 mainly decreased CD36 expression levels in the NAFLD liver tissues, which was confirmed at the protein and gene expression levels. In vitro, inhibition of PLD1 markedly decreased CD36 expression and lipid accumulation in SP treated AML12 cells. Furthermore, PA, the downstream product catalyzed by PLD1, increased the expression levels of CD36 and lipid accumulation in vitro, which was reversed by PPARγ antagonist. These suggested that PPARγ played an important role in transcriptional regulation of CD36 expression after PA stimulation. Finally, PLD inhibitor FIPI had significant therapeutic effect on HFD-induced NAFLD. Conclusion: Hepatocyte-specific deficiency of PLD1 ameliorates lipid accumulation and NAFLD development by inhibiting PPARγ/CD36 pathway conducted by PA.
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