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A microenvironment-inspired synthetic 3D model for pancreatic ductal adenocarcinoma organoids - Pancreas matrisome atlas

ABSTRACT: LC-MS/MS based analysis of the normal pancreas matrisome from 10 C57-Black6 animals. Matrisome abundance was quantified using a label-free quantification approach.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Epithelial Cell, Pancreas

SUBMITTER: Christopher Below

LAB HEAD: Claus Jorgensen

PROVIDER: PXD022555 | Pride | 2021-11-29

REPOSITORIES: Pride

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			Action	DRS
	041719_CB_P1E17_III_1_1_100ng.raw	Raw
	041719_CB_P1E17_III_1_2_100ng.raw	Raw
	041719_CB_P1E17_III_1_3_100ng.raw	Raw
	041719_CB_P1E17_III_1_4_100ng.raw	Raw
	041719_CB_P1E17_III_1_5_100ng.raw	Raw

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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-naÃ¯ve 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 OpâOp using a pairwise design corresponding to the cage experiment in the reference lake Opasatica (Op), comparison between fish Du and DuâDu 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 (OpâDu) and fish from reference lake caged in their own lake (OpâOp) using pairwise design corresponding to the experiment of metal contamination, comparison between fish from metal contaminated lake transplanted to the reference lake (DuâOp) and fish from the metal contaminated lake caged in their own lake (DuâDu) using pairwise design corresponding to the depuration experiment.

Project description:Our main objectives were: 1) to identify transcriptional signatures specific to the exposure to two metals: Ni and Cd; 2) to investigate the mechanisms of toxicity for these two metals; and 3) to develop a predictive tool to identify the sublethal effects of Ni and Cd contaminants in fish sampled from natural environments. The molecular mechanisms underlying nickel (Ni) and cadmium (Cd) toxicity and their specific effects on fish are poorly understood. Documenting gene transcription profiles offers a powerful approach towards identifying the molecular mechanisms affected by these metals and to discover biomarkers of their toxicity. However, confounding environmental factors can complicate the interpretation of the results and the detection of biomarkers for fish captured in their natural environment. In the present study, a 1000 candidate-gene microarray, developed from a previous RNA-seq study on a subset of individual fish from contrasting level of metal contamination, was used to investigate the transcriptional response to metal (Ni and Cd) and non metal (temperature, oxygen, and diet) stressors in yellow perch (Perca flavescens). Specifically, we aimed at 1) identifying transcriptional signatures specific to Ni and Cd exposure, 2) investigating the mechanisms of their toxicity, and 3) developing a predictive tool to identify the sublethal effects of Ni and Cd contaminants in fish sampled from natural environments. A total of 479 genes displayed significantly different transcription levels when temperature varied while 287 and 177 genes were differentially transcribed at different concentrations of Ni and Cd, respectively. These metals were found to mainly affect the transcription level of genes involved in iron metabolism, transcriptional and translational processes, vitamin metabolism, blood coagulation, and calcium transport. In addition, a linear discriminant analysis (LDA) made using gene transcription levels yielded 94% correctly reassigned samples regarding their level of metal contamination, which indicates the potential of the microarray to detect perch response to Cd or Ni effects. Comparison between fish exposed to three temperatures (11, 20, 28M-BM-0C) using a loop design, comparison between control fish and fich exposed to restrictive diet using a pairwise design, comparison between fish exposed to hypoxia and control fish, comparison between fish exposed to two concentrations of cadmium and control fish using a loop design, and comparison between fish exposed to two concentrations of nickel and control fish using a loop design.

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A microenvironment-inspired synthetic 3D model for pancreatic ductal adenocarcinoma organoids - Pancreas matrisome atlas

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