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Single-nucleus Multiome ATAC and Gene Expression analysis of the liver tissues from matrin-3 floxed and liver-specific knockout mice

ABSTRACT: Single-nucleus Multiome ATAC and Gene Expression analysis of the liver tissues from matrin-3 floxed and liver-specific knockout mice

PROVIDER: PRJNA1111897 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29045501_1.fastq.gz	Fastqsanger.gz
	SRR29045501_2.fastq.gz	Fastqsanger.gz
	SRR29045502.fastq.gz	Fastqsanger.gz
	SRR29045503.fastq.gz	Fastqsanger.gz
	SRR29045504_1.fastq.gz	Fastqsanger.gz

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Single-nucleus Multiome ATAC and Gene Expression analysis of the liver tissues from matrin-3 floxed and liver-specific knockout mice

Project description:Matrin-3 is an RNA-binding protein involved in the pathogenesis of human diseases. Here we examined the hepatic transcriptome and chromatin accessibility of high-fat-diet (Research Diets, Inc; D12492) fed mice. After quality control filtering and removal of putative doublets, single-nucleus RNA-seq clusters were assigned to five different cell types, including hepatocytes (Hep), Kupffer cells (KC), endothelial cells (EC), hepatic stellate cells (HSC), and leukocytes (Leuk). The total number of cells is 1,543. Differential analysis of single-nucleus RNA-seq data identified 492 DEGs (FDR < 0.05 & fold change > 1.5) in the hepatocyte cluster between matrin-3 floxed and liver-specific knockout (LKO) mice. GSEA revealed that KEGG terms such as “Drug metabolism cytochrome P450” and “Metabolism of xenobiotics by cytochrome P450” were enriched in hepatocytes

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Project description:Matrin-3 is an RNA-binding protein involved in the pathogenesis of human diseases. Here we examined its previously uncharacterized role in limiting hepatic steatosis and stress response via the constitutive androstane receptor. Matrin-3 expression was induced in the steatotic livers of mice and humans. Liver-specific matrin-3 knockout (LKO) exacerbated high-fat diet (HFD)-induced steatosis, acute phase response, and inflammation in the liver of mice. Bulk RNA-seq and bioinformatics analysis identified 1,333 and 239 differentially expressed genes (fold change > 1.5 & Padj < 0.05), respectively in the livers of female and male matrin-3 LKO mice. Gene Set Enrichment Analysis revealed that the top most enriched Gene Ontology Biological Process was the “Xenobiotic metabolic process” in female matrin-3 floxed mice that is downregulated. The top two enriched biological processes are “Acute inflammatory response” and “Acute phase response” in the liver of female LKO mice that are upregulated. Several GO terms related to lipid metabolism and xenobiotic metabolism were enriched in the livers of male mice. Real-time qPCR revealed that the expression of many genes involved in xenobiotic metabolism was reduced in the liver of female LKO mice and to a lesser extent in the liver of male LKO mice, while the expression of acute-phase response genes was induced in the liver of female but not male LKO mice. Our data demonstrated that liver-specific matrin-3 deficiency re-programs the hepatic transcriptome enriched for xenobiotic metabolism pathway, acute-phase and inflammatory response signaling in the liver of HFD-fed mice.

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