Ontology highlight
ABSTRACT:
PROVIDER: PRJNA989546 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25116178_1.fastq.gz | Fastqsanger.gz | |||
| SRR25116178_2.fastq.gz | Fastqsanger.gz | |||
| SRR25116179_1.fastq.gz | Fastqsanger.gz | |||
| SRR25116179_2.fastq.gz | Fastqsanger.gz | |||
| SRR25116180_1.fastq.gz | Fastqsanger.gz |
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Project description:Innate immune cells sense microbial danger signals such as bacterial lipopolysaccharide (LPS) through pattern recognition receptors, resulting in dynamic transcriptional reprogramming and rapid inflammatory responses. If not properly regulated, such responses can be detrimental to the host, as is seen in septic shock. A better understanding of the genetic regulation of transcriptional responses during endotoxemia could provide potential therapeutic insights. However, the majority of animal model studies have been performed using classic inbred laboratory strains of mice, typically C57BL/6 (B6), capturing limited genetic diversity and representing a potential blind spot. Here, we compared classic inbred B6 mice with wild-derived and genetically divergent PWD/PhJ (PWD) mice using in vivo and in vitro models of endotoxemia, to determine the role of natural genetic variation in septic shock. Compared with B6 mice, PWD mice were markedly resistant to LPS-induced endotoxic shock. Using LPS stimulation of bone marrow derived dendritic cells (BMDC) and RNA sequencing, we demonstrate that B6 and PWD BMDCs exhibit partially overlapping, yet highly divergent transcriptional responses, with B6 skewed towards stereotypical proinflammatory pathway activation, and PWD engaging regulatory or developmental pathways. To dissect genetic regulation of inflammatory responses by allelic variants, we used BMDCs from a sub-consomic strain carrying a ~50 Mb PWD-derived portion of chromosome 11 on a B6 background. This identified a subset of cis regulated and a large number of trans regulated genes. Bioinformatic analyses identified candidate trans regulators encoded in the chromosome 11 locus as transcription factors Irf1, Ncor1, and Srebf1. Taken together, our results demonstrate that natural genetic variation exerts a pronounced effect on host survival and transcriptional reprogramming during endotoxemia, suggesting possibilities for prediction of sepsis risk and/or personalized therapeutic interventions.
2024-12-31 | GSE272206 | GEO
Project description:Interventions: Open label Phase 1b proof of concept study to test for dysbiosis in small cohort of people identified as at risk for developing colorectal cancer (CRC) based on the background of conventional adenomatous polyps, and the potential of a light infection with hookworm to improve microbial richness and diversity.
All participants will receive in total 20 hookworm larvae (L3) to be applied by the study nurse as two doses of 10x L3 to the skin approximately 4 weeks apart. The L3 will be applied to a non-adherent dressing which will be placed on the forearm of the participant. The dressing will need to remain in place for the remainder of the day, and disposed of at night.
Analyses of blood and rectal mucosal immune responses, mucosal and faecal microbiomes will be undertaken pre and 12 months post hookworm infection.
The fidelity of the hookworm intervention will be monitored by participant reported incidence of a rash at the inoculation site (the first week after inoculation) and laboratory tests for the typical immune response (eosinophilia) and the presence of parasite eggs in faecal samples taken at the post-inoculation clinic visits.
Primary outcome(s): A composite primary outcome including measurements of bacterial species richness (number of observed operational taxonomic units, OTUs) and bacterial species diversity (Shannon Index) in faecal and colon biopsy specimens, determined by shotgun metagenomic sequencing[Week 52 post hookworm inoculation]
Study Design: Purpose: Prevention; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Efficacy
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Project description:Using influenza A virus (IAV) infection in a mouse model of naturally selected genetic diversity, namely C57BL6/J (B6) mice carrying chromosomes (Chr) derived from the wild-derived and genetically divergent PWD/PhJ (PWD) mouse strain (B6.ChrPWD consomic mice), we examined the effects of genotype and sex on severity of IAV-induced disease To determine the role of genetic variation of host during IAV infection on gene expression, we performed RNAseq analysis on whole lung RNA isolated from two different mice.
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Project description:The collaborative cross (CC) founder strains include five classical inbred laboratory strains (129S1/SvlmJ, A/J, C57BL/6J (B6), NOD/ShiLtJ, and NZO/HILtJ) and three wild-derived strains (CAST/EiJ, PWK/PhJ (PWK) and WSB/EiJ) The strains encompass 89% of the genetic diversity available in Mus musculus and about 10 to 20 times more genetic diversity than found in Homo sapiens. For more than 60 years the B6 strain has been used as the model strain for high ethanol preference/high consumption. However, another one of the CC founder strains, PWK, was identified as a high ethanol preference/high consumption strain. The current study determined how the transcriptomes of the B6 and PWK strains differed from the 6 low preference CC strains across 3 nodes of the brain addiction circuit. RNA-Seq data were collected from the central nucleus of the amygdala, the nucleus accumbens core and the prelimbic cortex. Differential expression (DE) analysis was performed in each of these brain regions for all 28 possible pairwise comparisons of the CC founder strains. Unique genes for each strain were identified by selecting for genes that differed significantly (false discovery rate (FDR) < 0.05) from all other strains in the same direction. B6 was identified as the most distinct inbred laboratory strain, having the highest number of total differently expressed genes (DEGs) and DEGs with high log fold change, and unique genes compared to other CC strains. Less than 50 unique DEGs were identified in common between B6 and PWK within all three brain regions, indicating the strains potentially represent two distinct genetic signatures for risk for high ethanol-preference. 238 DEGs were found to be commonly different between B6, PWK and the average expression of the remaining CC strains within all three regions. The commonly different up-expressed genes were significantly enriched (FDR < 0.001) among genes associated with neuroimmune function. These data compliment the observation that neuroimmune signaling is key to understanding alcohol use disorder and and support use of these 8 strains and the highly heterogeneous mouse populations derived from them to identify alcohol-related brain mechanisms and treatment targets.
2022-08-27 | GSE212000 | GEO
Project description:Microbial diversity after inoculation with RP01
| PRJNA940313 | ENA
Project description:In this study, mouse microbial populations were depleted using an antibiotic cocktail. The microbiome was reestablished using fecal matter transplant or single-strain bacteria species. Volatile organic compounds emitted from the mice were screened to determine if the diversity of the microbial populations can alter host volatilome.
2023-10-16 | MSV000093123 | MassIVE
Project description:Identify genes in liver tissue whose expression is under genetic and high fat diet induced regulation in three Chromosome 1 substitution lines derived from Chinese wild mice (B6-Chr1SJ (SJ), B6-Chr1KM (KM), and B6-Chr1HZ (HZ)) and one donor strain C57B/LJ(B6) We used microarrays to detail the global gene expression in three chromosome 1 substitution lines and one donor strain which fed with control or high fat diet.
2016-05-04 | GSE81078 | GEO