Ontology highlight
ABSTRACT:
PROVIDER: PRJNA596986 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10744552_1.fastq.gz | Fastqsanger.gz | |||
| SRR10744552_2.fastq.gz | Fastqsanger.gz | |||
| SRR10744553_1.fastq.gz | Fastqsanger.gz | |||
| SRR10744553_2.fastq.gz | Fastqsanger.gz | |||
| SRR10744554_1.fastq.gz | Fastqsanger.gz |
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Project description:Our main objectives wereto investigate the molecular mechanisms involved in metal toxicity and detoxification in the field using juvenile yellow perch subjected to differents levels of this metal exposure. Recent local adaptation to pollution has been evidenced in several organisms inhabiting environments heavily contaminated by metals. Nevertheless, the molecular mechanisms underlying adaptation to high metal concentrations are poorly understood, especially in fishes. Yellow perch (Perca flavescens) populations from lakes in the mining area of Rouyn-Noranda (QC, Canada) have been faced with metal contamination for about 90 years. Here, we examine gene transcription patterns of fish reciprocally transplanted between a reference and a metal-contaminated lake and also fish caged in their native lake. After four weeks, 111 genes were differentially transcribed in metal-naïve fish transferred to the metal-contaminated lake, revealing a plastic response to metal exposure. Genes involved in the citric cycle and beta-oxidation pathways were under-transcribed, suggesting a potential strategy to mitigate the effects of metal stress by reducing energy turnover. However, metal-contaminated fish transplanted to the reference lake did not show any transcriptomic response, indicating a reduced plastic response capability to sudden reduction in metal concentrations. Moreover, the transcription of other genes, especially ones involved in energy metabolism, was affected by caging. Overall, our results highlight environmental stress response mechanisms in yellow perch at the transcriptomic level and support a rapid adaptive response to metal exposure through genetic assimilation. Comparison between fish Op and Op→Op using a pairwise design corresponding to the cage experiment in the reference lake Opasatica (Op), comparison between fish Du and Du→Du using a pairwise design corresponding to the cage experiment in the metal contaminated lake Dufault (Du), comparison between fish from reference lake transplanted to the metal contaminated lake (Op→Du) and fish from reference lake caged in their own lake (Op→Op) using pairwise design corresponding to the experiment of metal contamination, comparison between fish from metal contaminated lake transplanted to the reference lake (Du→Op) and fish from the metal contaminated lake caged in their own lake (Du→Du) using pairwise design corresponding to the depuration experiment.
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Figure 4c, obtained from the simulation of human colitis model is highlighted here.
This model is described in the article:
Kilian, C., Ulrich, H., Zouboulis, V.A. et al. Longitudinal single-cell data informs deterministic modelling of inflammatory bowel disease. npj Syst Biol Appl 10, 69 (2024). https://doi.org/10.1038/s41540-024-00395-9
Abstract:
Single-cell-based methods such as flow cytometry or single-cell mRNA sequencing (scRNA-seq) allow deep molecular and cellular profiling of immunological processes. Despite their high throughput, however, these measurements represent only a snapshot in time. Here, we explore how longitudinal single-cell-based datasets can be used for deterministic ordinary differential equation (ODE)-based modelling to mechanistically describe immune dynamics. We derived longitudinal changes in cell numbers of colonic cell types during inflammatory bowel disease (IBD) from flow cytometry and scRNA-seq data of murine colitis using ODE-based models. Our mathematical model generalised well across different protocols and experimental techniques, and we hypothesised that the estimated model parameters reflect biological processes. We validated this prediction of cellular turnover rates with KI-67 staining and with gene expression information from the scRNA-seq data not used for model fitting. Finally, we tested the translational relevance of the mathematical model by deconvolution of longitudinal bulk mRNA-sequencing data from a cohort of human IBD patients treated with olamkicept. We found that neutrophil depletion may contribute to IBD patients entering remission. The predictive power of IBD deterministic modelling highlights its potential to advance our understanding of immune dynamics in health and disease.
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