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BMC genomics2017; 18(1); 34; doi: 10.1186/s12864-016-3390-y

LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells.

Abstract: Lipopolysaccharide (endotoxin, LPS) is a strong inducer of the innate immune response. It is widespread in our environment, e.g. in house dust and contributes to asthma. Compared to humans, horses are even more sensitive to LPS. However, data on LPS effects on the equine transcriptome are very limited. Using RNA-seq we analysed LPS-induced differences in the gene expression in equine peripheral blood mononuclear cells at the gene and gene-network level in two half-sib families and one group of unrelated horses. 24 h-LPS challenge of equine immune cells resulted in substantial changes in the transcriptomic profile (1,265 differentially expressed genes) showing partial overlap with human data. One of the half-sib families showed a specific response different from the other two groups of horses. We also identified co-expressed gene modules that clearly differentiated 24 h-LPS- from non-stimulated samples. These modules consisted of 934 highly interconnected genes and included genes involved in the immune response (e.g. IL6, CCL22, CXCL6, CXCL2), however, none of the top ten hub genes of the modules have been annotated as responsive to LPS in gene ontology. Using weighted gene co-expression network analysis we identified ten co-expressed gene modules significantly regulated by in vitro stimulation with LPS. Apart from 47 genes (5%) all other genes highly interconnected within the most up- and down-regulated modules were also significantly differentially expressed (FDR < 0.05). The LPS-regulated module hub genes have not yet been described as having a role in the immune response to LPS (e.g. VAT1 and TTC25).
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Publication Date: 2017-01-05 PubMed ID: 28056766PubMed Central: PMC5217269DOI: 10.1186/s12864-016-3390-yGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates how lipopolysaccharide (LPS), a strong stimulator of the immune response, affects the gene expression in horses’ peripheral blood mononuclear cells. By analyzing RNA sequences, the researchers identified several gene co-expression networks significantly affected by LPS stimulation.

Study Background

  • The study revolves around Lipopolysaccharide (LPS), an endotoxin known to trigger the innate immune response. This substance is commonly found in environments such as house dust and thus has a significant impact on health conditions like asthma. The researchers noted that horses are even more sensitive to LPS in comparison to humans.
  • Despite this sensitivity, there is limited data on how LPS affects the equine (horses’) transcriptome – the complete set of transcripts in a cell, which offers more understanding of genetic activity.

Research Methodology and Results

  • The researchers used RNA sequencing to examine differences in gene expression induced by LPS in equine peripheral blood mononuclear cells. Consideration was given to both gene and network levels across two half-sib families and a group of unrelated horses.
  • Stimulation of equine immune cells with LPS for 24 hours resulted in significant changes to the transcriptomic profile, with 1,265 differentially expressed genes identified. Some of these changes were found to partially overlap with previous data on humans.
  • One of the half-sib families exhibited a distinct response compared to the other groups of horses studied.
  • The study also discovered co-expressed gene modules (sets of genes expressed together) differentiating LPS-stimulated samples from non-stimulated ones.

Co-expressed Gene Modules

  • The co-expressed gene modules consisted of 934 highly interconnected genes, including those involved in immune response (e.g., IL6, CCL22, CXCL6, CXCL2). However, none of the top ten hub genes in these modules were previously annotated as being responsive to LPS according to gene ontology.
  • Using weighted gene co-expression network analysis (a method for describing the correlation patterns among genes), the team uncovered ten co-expressed gene modules that were significantly regulated by in vitro (in a controlled lab setting) LPS stimulation.
  • 47 out of these genes were highly interconnected within the most upregulated and down-regulated modules, and they were also significantly differentially expressed. Conversely, the hub genes of the LPS-regulated modules (such as VAT1 and TTC25) have not been previously linked to immune response to LPS.

Cite This Article

APA
Pacholewska A, Marti E, Leeb T, Jagannathan V, Gerber V. (2017). LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells. BMC Genomics, 18(1), 34. https://doi.org/10.1186/s12864-016-3390-y

Publication

BMC genomics
ISSN: 1471-2164
NlmUniqueID: 100965258
Country: England
Language: English
Volume: 18
Issue: 1
Pages: 34
PII: 34

Researcher Affiliations

Pacholewska, Alicja
  • Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern, and Agroscope, Länggassstrasse 124, 3012, Bern, Switzerland. alicja@rth.dk.
  • Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012, Bern, Switzerland. alicja@rth.dk.
Marti, Eliane
  • Department of Clinical Research and Veterinary Public Health, Division of Experimental Clinical Research, Vetsuisse Faculty, University of Bern, Länggassstrasse 124, 3012, Bern, Switzerland.
Leeb, Tosso
  • Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012, Bern, Switzerland.
Jagannathan, Vidhya
  • Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012, Bern, Switzerland.
Gerber, Vincent
  • Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern, and Agroscope, Länggassstrasse 124, 3012, Bern, Switzerland.

MeSH Terms

  • Animals
  • Cluster Analysis
  • Computational Biology / methods
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Ontology
  • Gene Regulatory Networks
  • Genetic Background
  • Horses
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharides / immunology
  • Transcriptome

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