LPS Administration Impacts Glial Immune Programs by Alternative Splicing.

Vladimir N Babenko,Galina T Shishkina,Ekaterina V Sukhareva,Dmitriy A Lanshakov,Nikolay N Dygalo

doi:10.3390/biom12020277

Vladimir N Babenko, Galina T Shishkina + Show 3 more

Open Access

https://doi.org/10.3390/biom12020277

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Journal: Biomolecules	Publication Date: Feb 8, 2022
Citations: 4	License type: CC BY 4.0

Affiliation: Institute of Cytology and Genetics

Abstract

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.

Highlights

An increasing interest in the study of neuroinflammation is explained by its association with different neurodegenerative diseases
Clustering algorithm GOMCL (Wang et al, 2020), which yielded just one gene ontology (GO) supercluster consisting of 37 distinct differentially expressed genes (DEGs), encompassing the 284-fold initial GO BP annotation list (Table S1, Supplementary Materials)
We identified the gene as a cell specific on when it maintains the highest expression among seven cell types

Summary

Introduction

An increasing interest in the study of neuroinflammation is explained by its association with different neurodegenerative diseases. In order to understand the molecular changes that contribute to the development of these diseases, lipopolysaccharide (LPS), the component of the outer membrane of Gram-negative bacteria, is widely used for induction of the central inflammatory process [2]. Injections of LPS resulted in gene expression changes in brain structures, including the hippocampus [3], brain region that was implicated in the development of neurodegenerative-related psychopathology. Alternative splicing manifests the flexible and rapidly evolving mechanism [4,5] of expanding the proteome diversity. Neuroinflammation related CD44 alternative splicing was shown to affect the response of the hippocampus in the Alzheimer disease [6].

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