Biology subjects

Gerber, V.

Publications and source records attributed to Gerber, V..

4 recordsLinked to original sources

bioRxiv2023

Single-cell profiling of bronchoalveolar cells reveals a Th17 signature in neutrophilic severe equine asthma

Severe equine asthma (SEA) shares clinical and pathological features with human neutrophilic asthma, serving as a rare natural model for this condition. To uncover the elusive immune mechanisms driving SEA, we performed single-cell mRNA sequencing (scRNA-seq) on cryopreserved bronchoalveolar cells from 11 Warmblood horses, five controls and six with SEA. We identified six major cell types, showing significant heterogeneity and novel subtypes. Notably, we observed monocyte-lymphocyte complexes and detected a robust Th17 signature in SEA, with CXCL13 upregulation in intermediate monocytes. Asthmatic horses exhibited expansion of the B cell population, Th17 polarization of the T cell populations, and dysregulation of genes associated with T cell function. Neutrophils demonstrated enhanced migratory capacity and heightened aptitude for neutrophil extracellular trap formation. These findings provide compelling evidence for a predominant Th17 immune response in neutrophilic SEA, driven by dysregulation of monocyte and T cell genes. The dysregulated genes identified through scRNA-seq have potential as biomarkers and therapeutic targets for SEA and provide insights into human neutrophilic asthma. One Sentence SummarySingle-cell mRNA sequencing identifies a predominant Th17-mediated immune response in severe equine asthma

immunology↗

bioRxiv2019

Effects of breed, management and personality on cortisol reactivity in sport horses

Sport horses need to fulfill high physical and psychological requirements during training and competition. These as well as certain conditions of modern husbandry may affect their wellbeing. Here we aimed to (1) evaluate effects of demographic and management factors as well as personality traits on stress reactivity of sport horses, (2) investigate if elite sport horses have elevated stress levels compared to amateur sport horses, and (3) assess whether different equestrian disciplines differentially influence horses adrenal cortex responsiveness. For this purpose, we visited 149 healthy elite (n=94) and amateur (n=54) sport horses in Switzerland and performed an adrenocorticotropic hormone (ACTH) stimulation test. Additionally, a person who was familiar with the horse completed a questionnaire about demographic and management factors and horses personality traits. Linear models were calculated to assess associations between the questionnaire data and salivary cortisol 60 and 90 minutes after ACTH stimulation. While the model at T90 was not significant, post-stimulatory cortisol after 60 min appears most informative in line with a previous study and was significantly affected by the horses breed and by three management factors: "number of riders", "hours spent outside" and "group housing" (adjusted r2 =15%, p<0.001). Thoroughbred and Warmblood horses displayed an increased adrenal response compared to Franches-Montagnes horses. Horses with several riders had a less pronounced reaction than horses with one rider, and horses that spent more time outside had a decreased response compared to horses that were stabled most of the time. Horses living in groups showed higher post-stimulatory cortisol values than horses that were housed singly. However, no significant associations of cortisol responsiveness with personality traits were found, and neither the horses use as elite or as amateur sport horses nor the discipline had an effect on the cortisol response. This suggests that optimizing husbandry conditions may be more important for improving horses welfare than changing their use.

animal behavior and cognition↗

bioRxiv2019

PBMC Treatment Significantly Changes Gene Expression Regulation in Horses

Expression quantitative trait loci (eQTLs) are context dependent, and therefore change between tissues, cell types, and after cell treatment. In addition, SNP positions and RNAseq counts must be updated after assembly of new reference genome sequences. Therefore, we remapped eQTLs with Matrix eQTL using the previously generated and publicly available data from four contexts of peripheral blood mononuclear cells (PBMCs) from European Warmblood horses to the EquCab3.0 reference genome, and used a linear mixed model in R to identify eQTLs with significantly different gene expression regulation in treated PBMCs when compared to no treatment (baseline). We found no evidence that SNPs associated with significant changes in gene expression between MCK and a treatment in PBMCs caused strong opposing regulatory effects. We identified canonical pathways with a significant number of genes in PBMCs with altered gene expression regulation when treated with lipopolysaccharides (LPS) and hay-dust extract (HDE). Significant pathways included RhoA signaling in LPS, as well as histamine degradation, cholesterol biosynthesis, Fc{gamma}RIIB signaling, and others in HDE. Our results support previous research indicating that pathways altered between baseline and treatment of PBMCs in horses with LPS or HDE affect inflammatory responses through RhoA, B-cell signaling, IL-4 and IFN-{gamma}, and histamine.

genomics↗

bioRxiv2017

Development of a high-density, 2M SNP genotyping array and 670k SNP imputation array for the domestic horse

BackgroundTo date, genome-scale analyses in the domestic horse have been limited by suboptimal single nucleotide polymorphism (SNP) density and uneven genomic coverage of the current SNP genotyping arrays. The recent availability of whole genome sequences has created the opportunity to develop a next generation, high-density equine SNP array.\n\nResultsUsing whole genome sequence from 153 individuals representing 24 distinct breeds collated by the equine genomics community, we cataloged over 23 million de novo discovered genetic variants. Leveraging genotype data from individuals with both whole genome sequence, and genotypes from lower-density, legacy SNP arrays, a subset of [~]5 million high-quality, high-density array candidate SNPs were selected based on breed representation and uniform spacing across the genome. Considering probe design recommendations from a commercial vendor (Affymetrix, now Thermo Fisher Scientific) a set of [~]2 million SNPs were selected for a next-generation high-density SNP chip (MNEc2M). Genotype data were generated using the MNEc2M array from a cohort of 332 horses from 20 breeds and a lower-density array, consisting of [~]670 thousand SNPs (MNEc670k), was designed for genotype imputation.\n\nConclusionsHere, we document the steps taken to design both the MNEc2M and MNEc670k arrays, report genomic and technical properties of these genotyping platforms, and demonstrate the imputation capabilities of these tools for the domestic horse.

genomics↗