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Sepsis-induced liver injury (SILI) indicates liver functional or structural impairment occurring during sepsis and is one of the common complications of sepsis. N6-methyladenosine (m6A) modification plays a significant role in the pathological processes of SILI, but its specific mechanisms remain unclear and require further elucidation. In this study, an experimental sepsis model exhibiting characteristic symptoms and hepatic damage was established through cecal ligation and puncture (CLP) surgery. Comprehensive analyses of hepatic tissues from CLP-treated and Sham operation mice through RNA Sequencing (RNA-Seq) and Methylated RNA Immunoprecipitation Sequencing (MeRIP-Seq) methodologies revealed distinct m6A peaks and differentially expressed genes (DEGs). A total of 2002 m6A peaks were detected (|log2FC|≥ 1, p < 0.05). Our analyses demonstrated that 71% of m6A peaks clustered within the coding sequences (CDS) and 3' untranslated region starts (3' UTR) of transcripts. When compared with the Sham group, the CLP group showed an increase of 1741 DEGs and a decrease of 1815 DEGs. And 458 genes exhibited both m6A modifications and changes in mRNA levels. Functional enrichment assessments through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that m6A-modified hepatic genes in septic mice were significantly enriched in the cytoplasm, nucleus and protein binding, which mainly involved in regulating cell survival, immune responses, inflammatory responses and other related pathways. The results of Cell Counting Kit-8 (CCK8) assay and 5-ethynyl-2'-deoxyuridine (EdU) assay showed that the proliferation ability of liver cell lines was enhanced after knocking down m6A regulatory factor METTL3, which indicates the m6A modifications play an important role in the proliferation ability of normal liver cells. This study validated the presence of m6A-epitranscriptomic modifications and their regulatory roles in sepsis-affected hepatic systems, establishing comprehensive m6A landscapes in septic liver tissues.
Pubmed ID: 40775729
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Software tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.
View all literature mentionsIntegrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsAn efficient software tool to utilize update-to-date information to functionally annotate genetic variants detected from diverse genomes (including human genome hg18, hg19, as well as mouse, worm, fly, yeast and many others). Given a list of variants with chromosome, start position, end position, reference nucleotide and observed nucleotides, ANNOVAR can perform: 1. gene-based annotation. 2. region-based annotation. 3. filter-based annotation. 4. other functionalities. (entry from Genetic Analysis Software)
View all literature mentionsGraph-based alignment of next generation sequencing reads to a population of genomes.
View all literature mentionsSoftware package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.
View all literature mentionsSoftware application for assembling of RNA-Seq alignments into potential transcripts. It enables improved reconstruction of a transcriptome from RNA-seq reads. This transcript assembling and quantification program is implemented in C++ .
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