Project description:In this study, we investigated the changes in phosphorylation of proteins in urinary extracellular vesicles from dogs with invasive urothelial carcinoma compared to control dogs.
Project description:Naturally occurring canine invasive urinary carcinoma (iUC) closely resembles human muscle invasive bladder cancer in terms of histopathology, metastases, response to therapy and, low survival rate. The heterogeneous nature of the disease has led to the association of large numbers of risk loci in humans, however most are of small effect. There exists a need for new and accurate animal models of invasive bladder cancer. In dogs, distinct breeds show markedly different rates of iUC, thus presenting an opportunity to identify additional risk factors and overcome the locus heterogeneity encountered in human mapping studies. In the association study presented here, inclusive of 100 Shetland sheepdogs and 58 dogs of other breeds, we identify a homozygous protein altering point mutation within the NIPAL1 gene which increases risk by eight-fold (OR=8.42, CI=3.12-22.71), accounting for nearly 30% of iUC risk in the Shetland sheepdog. Inclusion of six additional loci accounts for the majority of disease risk in the breed and explains nearly 75% of the phenotypes in this study. When combined with sequence data from tumors, we show that variation in the MAPK signaling pathway is an overarching cause of iUC susceptibility in dogs.
Project description:In dogs, a species for which markers of cell populations are often limiting, we sought to evaluate in an unbiased way the heterogeneity of cell subpopulations in the bronchoalveolar lavage fluid of healthy dogs, by single-cell RNA-sequencing.
Project description:Purpose: The transcriptome profiles were compared among groups of chronic stress exposure and control in two different breeds to identify genes and pathways related to response to chronic stress in the pituitary-adrenal axis. Methods: 6 male adult CFD and 6 Beagles were chosen at random with the similarities in good health, weight and other aspects. Separately, 3 of these two breeds were freely selected for the stress exposure via intermittent electrical stimulation and restraint stress, while the other 3 of these two breeds were non-disposed for normal control.The details for the disposal of dogs were: every morning dogs were restrained and electrical stimulations were exerted with a stable current of 10 mA for 6 s and then with a 6 s interval, lasting for 20 min every day. The duration of disposal was ten days.ll 12 dogs were killed by air embolism in the 11th day. Subsequently, pituitary and adrenal cortex tissues were fast collected and isolated for further high-sequencing. Results: 8 cDNA libraries were constructed for RNA-seq. A number of reads ranging from 53,295,978 to 65,414,932 was obtained in those 8 groups. About 10,000 genes and transcripts were annotated in each group. Besides,A total of 40, 346, 376, 69, 70, 38, 57, and 71 DEGs were detected in the contrasts of BP1_vs_BP2, CFDP1_vs_CFDP2, BP1_vs_CFDP1, BP2_vs_CFDP2, BAC1_vs_BAC2, CFDAC1_vs_CFDAC2, BAC1_vs_CFDAC1, and BAC2_vs_CFDAC2, respectively. Conclusions: Our results can contribute to a more comprehensive understanding about the genetic mechanisms of response to chronic stress in adrenal cortex and pituitary. Adrenal cortex and pituitary mRNA profiles of adult Chinese Field Dog and Beagle under chronic stress exposure and normal control, including BAC1 (Beagle adrenal cortex with disposal), BAC2 (Beagle adrenal cortex with non-disposal), BP1 (Beagle pituitary with disposal), BP2 (Beagle pituitary with non-disposal), CFDAC1 (Chinese Field Dog adrenal cortex with disposal), CFDAC2 (Chinese Field Dog adrenal cortex with non-disposal), CFDP1 (Chinese Field Dog pituitary with disposal), CFDP2 (Chinese Field Dog pituitary with non-disposal), were generated by deep sequencing, using Illumina Genome Analyzer IIx.
Project description:The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a zoonotic disease influenced human evolution, we studied changes in human expression of anthrax toxin receptor 2 (ANTXR2), which encodes a cell surface protein necessary for Bacillus anthracis virulence toxins to cause anthrax disease. In immune cells, ANTXR2 was 8-fold down-regulated in all available human samples compared to non-human primates, indicating regulatory changes early in the evolution of modern humans. We also observed multiple genetic signatures consistent with recent positive selection driving a European-specific decrease in ANTXR2 expression in several non-immune tissues affected by anthrax toxins. Our observations fit a model in which humans adapted to anthrax disease following early ecological changes associated with hunting and scavenging, as well as a second period of adaptation after the rise of modern agriculture.
2020-08-14 | GSE156161 | GEO
Project description:Midgut transcriptome assessment of the cockroach-hunting wasp Ampulex compressa (Apoidea: Ampulicidae)
Project description:We performed a single cell RNA-seq survey of 14,704 invasive fibroblasts and 16,104 non-invasive fibroblasts using an in vitro assay system which had been previously used to evaluate the ability of lung fibroblasts to spontaneously invade Matrigel and commonly used to analyze the metastatic potential of cancer cells. Different subtypes in invasive or non-invasive lung fibroblasts were classified, and their gene signatures, specific cell surface markers, long non-coding RNA (lncRNA), key transcription factors and signaling pathways were further confirmed mechanistically and functionally. After combination of all the specific genes for Ingenuity Pathway Analysis (IPA), we found that the ERBB2 (HER2) signaling pathway was significantly activated in invasive fibroblasts and was markedly inhibited in non-invasive fibroblasts.
Project description:Context : Non Functioning Pituitary Adenomas (NFPAs), although typically benign, may be locally invasive. Few datas are currently available related to the molecular process of invasion in sporadic pituitary adenomas. Markers of invasiveness, important for helping the clinician in the therapeutic strategy particularly in the decision for adjuvant radiotherapy, are currently lacking. Objective: Evaluate if invasive NFPAs display a specific expression profile compared with non invasive tumors. Methods: To address this issue, we selected 40 NFPAs (38 of the gonadotroph type) and classified them as invasive (n=22) or non invasive (n=18) on the basis of MRI and surgical findings. Then we performed pangenomic analysis based on Agilent Human Whole genome Gene Expression oligonucleotide microarray (44k) Expression in order to identify genes differentially expressed between invasive and non invasive NFPA. Experiements are made in dual color with tumor samples labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3.The expressions of some genes identified by microarray screening were confirmed by real-time quantitative RT-PCR. The selection of genes was made on the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors. Moreover, some genes of interest already described in the literature were added to the analysis. Results: Prediction class analysis showed that 346 genes discriminated between invasive and non invasive NFPAs (p<0.001); 233 were up- and 113 were down-regulated between the two groups. We then tested On the basis of Ingenuity networks and degree of upregulation between invasive and non invasive tumors, a set of eight genes, including MYO5A, IGFBP5, FLT3, NFE2L1, PTTG, MMP9, NCAM and NR1H3, was tested in quantitative PCR analysis and. Results confirmed those obtained in microarrays results.analysis. At the protein level, Myosin 5A (MYO5A) demonstrated stronger immunostaining in invasive NFPAs compared to non invasive NFPAs. Conclusions: We propose a molecular signature of eight genes of grossly invasive NFPAs as compared with non invasive tumors: The product of one of these genes, MYO5A, may be a useful marker of invasive process in tumoral specimens. The role of these genes in the invasiveness process and as prognostic markers of pituitary adenomas needs to be confirmedinvestigated. Method: Microarray analyses the transcriptome of 22 invasive Non Functional Pituitary Adenomas (NFPAs) and 18 non invasive NFPAs in dual color (each sample labelled in cyanine 5 and a pool of all tumors labelled in cyanine 3).