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LPS 给药通过选择性剪接影响神经胶质免疫程序。

LPS Administration Impacts Glial Immune Programs by Alternative Splicing.

机构信息

Laboratory of Functional Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia.

出版信息

Biomolecules. 2022 Feb 8;12(2):277. doi: 10.3390/biom12020277.

DOI:10.3390/biom12020277
PMID:35204777
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8961644/
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 gene, with skipping of exon 8 in LPS group. 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 isoform de-represses immune-specific response by adjusted splicing architecture. Additionally, the () immune-specific splicing factor has apparently been de-repressed by the short isoform in glial cells. Notably, both the and 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.

摘要

我们在脂多糖(LPS)给药后 24 小时对海马体进行了转录组分析。我们观察到了胶质细胞特异性基因,占所有差异表达基因(DEG)的三分之二。我们发现 LPS 组中小胶质细胞的 DEG 数量最多。相反,差异剪接(DAS)分析显示星形胶质细胞中 DAS 事件数量最多。此外,我们观察到 基因的主要同工型转换明显,LPS 组中第 8 个外显子缺失。根据先前的研究,通常被认为是大脑胚胎发育中维持多能性的物质。分析 LPS 暴露后的剪接调整,我们推测短的 同工型通过调整剪接结构来解除对免疫特异性反应的抑制。此外,在神经胶质细胞中,免疫特异性剪接因子 () 明显被短的 同工型解除抑制。值得注意的是,和 基因主要在小胶质细胞/内皮脑细胞中表达。我们还报告了免疫相关基因,它们在 LPS 暴露后改变其主要同工型。结果揭示了大脑中剪接的免疫调节作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/1b058eb99743/biomolecules-12-00277-g018.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/cea09b0c36b3/biomolecules-12-00277-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/7dcf8f219386/biomolecules-12-00277-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/d61a96a95545/biomolecules-12-00277-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/1b058eb99743/biomolecules-12-00277-g018.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/a62e69787484/biomolecules-12-00277-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/bd0e4d7dbe75/biomolecules-12-00277-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/7f8fb697d7d4/biomolecules-12-00277-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/f3ca7fe0a597/biomolecules-12-00277-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/1c1301584f80/biomolecules-12-00277-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/ab9e861efd32/biomolecules-12-00277-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/6762defa139d/biomolecules-12-00277-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/cea09b0c36b3/biomolecules-12-00277-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/0d89b128682a/biomolecules-12-00277-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/4912102102b3/biomolecules-12-00277-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/8e8d781f4c3d/biomolecules-12-00277-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/d0408d7a93f4/biomolecules-12-00277-g013a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/ebbaf844745f/biomolecules-12-00277-g014a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/2efd6122ff7d/biomolecules-12-00277-g015a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/7dcf8f219386/biomolecules-12-00277-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/d61a96a95545/biomolecules-12-00277-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23e9/8961644/1b058eb99743/biomolecules-12-00277-g018.jpg

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