LPS Administration Impacts Glial Immune Programs by Alternative Splicing.
Vladimir N BabenkoGalina T ShishkinaDmitriy A LanshakovEkaterina V SukharevaNikolay N DygaloPublished in: Biomolecules (2022)
We performed transcriptome analysis in the hippocampus 24 h after lipopolysaccharide (LPS) administration. We observed glial-specific genes, comprised of two-thirds of all differentially expressed genes (DEGs). We found microglial DEGs that were the most numerous in LPS group. On the contrary, differential alternative splicing (DAS) analysis revealed the most numerous DAS events in astrocytes. Besides, we observed distinct major isoform switching in the Ptbp1 gene, with skipping of exon 8 in LPS group. Ptbp1 usually considered a pluripotency sustaining agent in brain embryonic development, according to the previous studies. Analyzing the splicing tune-up upon LPS exposure, we came to a supposition that the short Ptbp1 isoform de-represses immune-specific response by Ptbp1 adjusted splicing architecture. Additionally, the Ptbp3 ( NOD1 ) immune-specific splicing factor has apparently been de-repressed by the Ptbp1 short isoform in glial cells. Notably, both the Ptbp1 and Ptbp3 genes express primarily in microglial/endothelial brain cells. We also report immune-related genes, altering their major isoforms upon LPS exposure. The results revealed immune modulating role of alternative splicing in brain.
Keyphrases
- inflammatory response
- anti inflammatory
- lipopolysaccharide induced
- lps induced
- genome wide
- induced apoptosis
- neuropathic pain
- toll like receptor
- resting state
- white matter
- genome wide identification
- cell cycle arrest
- cerebral ischemia
- signaling pathway
- functional connectivity
- single cell
- public health
- disease activity
- cell death
- dna methylation
- gene expression
- spinal cord injury
- systemic lupus erythematosus
- bioinformatics analysis
- oxidative stress
- multiple sclerosis
- endoplasmic reticulum stress
- data analysis