Kennel Club Genetics Centre Canine WGS Analysis
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PROVIDER: PRJEB36029 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gene expression patterns of bronchiolar progenitors and club cells in mouse lung were examined by microarray experiments. Although it has not yet been fully characterized, a subset of epithelial cells lining bronchioles are best understood as bronchiolar progenitors that self-renew over the long term and that can differentiate into more differentiated club cells and ciliated cells. The bronchiolar progenitors are distinct from club cells and characteristically express the alveolar type 2 cell marker, prosurfactant protein C, with lower levels of club cell secretory protein/Scgb1a1. There are also functional differences between them; while club cells can be depleted by naphthalene because of the abundance of cytochrome P450 enzyme Cyp2f2, bronchiolar progenitors are resistant to naphthalene-induced depletion because of defects in the enzyme.
2016-02-17 | E-MTAB-4460 | biostudies-arrayexpress
Project description:To facilitate canine proteomics research, we have generated a non-redundant canine protein sequence database, with entry name annotation based on sequence similarity to the human proteome. To evaluate the sequence-based annotation transfer, we performed a shotgun proteomics experiment on subcellular fractions of canine spleen.
2022-03-02 | PXD003847 | Pride
Project description:Lung adenocarcinoma (LUAD) is one of the deadliest malignancies worldwide. Dynamic lineage changes within the lung epithelium and the high plasticity of these epithelial cells confound the correct identification of the cell-of-origin of LUAD. Here, we combined lineage-tracing mouse models with an autochthonous cell type-independent LUAD model in order to discover the cellular origin of ALK-translocated LUAD. We identified Club and AT2 cells as the cells-of-origin of LUAD. Moreover, we uncovered epigenetic imprints in the tumours originating from Club or AT2 cells by whole-genome bisulfite sequencing. Single-cell transcriptomes of Club cells at different stages of tumour development identified two trajectories of Club cell evolution. On both routes, tumours lose their Club cell identity and gain an AT2-like phenotype. Together, this study highlights the role of Club cells in LUAD initiation and unveils key mechanisms conferring LUAD heterogeneity.
2022-06-30 | GSE176185 | GEO
Project description:Lung adenocarcinoma (LUAD) is one of the deadliest malignancies worldwide. Dynamic lineage changes within the lung epithelium and the high plasticity of these epithelial cells confound the correct identification of the cell-of-origin of LUAD. Here, we combined lineage-tracing mouse models with an autochthonous cell type-independent LUAD model in order to discover the cellular origin of ALK-translocated LUAD. We identified Club and AT2 cells as the cells-of-origin of LUAD. Moreover, we uncovered epigenetic imprints in the tumours originating from Club or AT2 cells by whole-genome bisulfite sequencing. Single-cell transcriptomes of Club cells at different stages of tumour development identified two trajectories of Club cell evolution. On both routes, tumours lose their Club cell identity and gain an AT2-like phenotype. Together, this study highlights the role of Club cells in LUAD initiation and unveils key mechanisms conferring LUAD heterogeneity.
2022-06-30 | GSE176184 | GEO
Project description:In this study, we present the first comparison of global transcriptional changes taking place in canine lymphoma and human diffuse large B-cell lymphoma (DLBCL), with particular reference to the nuclear factor-kappaB (NF-κB) pathway. Microarray data generated from lymph nodes diagnosed with canine DLBCL and healthy lymph nodes were used for differential expression analysis, co-expression analysis and pathway analysis, and compared with analysis of publicly available microarray data from human healthy and DLBCL lymph nodes. The comparisons between species at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa. A considerable number of differentially expressed genes between canine lymphoma and healthy lymph node samples were also found differentially expressed between human DLBCL and healthy lymph node samples. Principal component analysis (PCA) using a literature derived 120 NF-κB target gene set mapped to 199 orthologous canine array probesets and 259 human array probesets clearly separated the healthy and cancer samples in both canine and human datasets. The analysis demonstrated that for both human and canine DLBCL there is activation of the NF-κB/p65 canonical pathway rather than the alternative pathway. This has therapeutic implications for the use of specific pathway inhibitors for the treatment of DLBCL for both species and also indicates that naturally occurring canine lymphoma could be used as a model to study therapeutic strategies for human lymphoma. The model was further validated by the identification of molecular signatures that could sub-classify canine DLBCL into activated B-cell-like (ABC) or germinal centre B-cell-like (GCB) types equivalent to human subtypes.
2013-09-26 | GSE30881 | GEO
Project description:The club cell, a small airway epithelial (SAE) secretory cell that uniquely expresses SCGB1A1, plays a central role in host defense in the human lung. Based on data demonstrating that ~50% of club cells express MUC5B, a secretory mucin critical for mucociliary clearance, we hypothesized that subpopulations of club cells with distinct functions may exist. To evaluate this, the SAE of normal nonsmokers and healthy cigarette smokers was sampled by bronchoscopy and brushing followed by single cell sequencing using Drop-seq technology. Subpopulations of SCGCB1A1+KRT5loMUC5AC- club cells were assessed by unsupervised clustering to evaluate club cell subpopulations. Immunostaining of SAE in lung sections, brushed SAE cells, and in vitro air-liquid interface culture was utilized to confirm the transcriptomic-based observations. Unsupervised clustering of SCGCB1A1+KRT5loMUC5AC‾ club cells in the SAE identified 3 unique club cell populations that differed by differentiation state and function, including: (1) progenitor; (2) proliferating; and (3) effector subpopulations. The progenitor club cell population was energetically active with high expression of mitochondrial and ribosomal proteins and the highest KRT5 levels vs other club cell populations. The proliferating population, defined by high expression of cyclins and proliferation markers, was the smallest, representing 2% of club cells. The effector club cell cluster expressed transcripts for host defense genes, xenobiotic metabo-lism, and barrier functions commonly associated with club cell function. Comparison of the club cell subpopulations in smokers vs nonsmokers demonstrated that the proportion of the club cell effector population was significantly decreased in smokers with a concomitant significant in-crease in the proliferating cell population. These observations provide novel insights into both the makeup of human SAE club cell subpopulations and smoking-induced changes in club cell biology.
2021-09-22 | GSE155515 | GEO
Project description:In this study, we present the first comparison of global transcriptional changes taking place in canine lymphoma and human diffuse large B-cell lymphoma (DLBCL), with particular reference to the nuclear factor-kappaB (NF-?B) pathway. Microarray data generated from lymph nodes diagnosed with canine DLBCL and healthy lymph nodes were used for differential expression analysis, co-expression analysis and pathway analysis, and compared with analysis of publicly available microarray data from human healthy and DLBCL lymph nodes. The comparisons between species at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa. A considerable number of differentially expressed genes between canine lymphoma and healthy lymph node samples were also found differentially expressed between human DLBCL and healthy lymph node samples. Principal component analysis (PCA) using a literature derived 120 NF-?B target gene set mapped to 199 orthologous canine array probesets and 259 human array probesets clearly separated the healthy and cancer samples in both canine and human datasets. The analysis demonstrated that for both human and canine DLBCL there is activation of the NF-?B/p65 canonical pathway rather than the alternative pathway. This has therapeutic implications for the use of specific pathway inhibitors for the treatment of DLBCL for both species and also indicates that naturally occurring canine lymphoma could be used as a model to study therapeutic strategies for human lymphoma. The model was further validated by the identification of molecular signatures that could sub-classify canine DLBCL into activated B-cell-like (ABC) or germinal centre B-cell-like (GCB) types equivalent to human subtypes. Canine DLBCL patients were recruited via the clinical oncology service of the University of Edinburgh Royal (Dick) School of Veterinary Studies (DJA), and the University of Wisconsin-Madison School of Veterinary Medicine (DMV). Lymph node biopsy samples were taken, as part of normal diagnostic procedures, from dogs newly diagnosed with lymphoma (naïve) and samples from dogs that had relapsed following standard of care CHOP chemotherapy. Only dogs with confirmed DLBCL after pathological grading were used in this study. This included standard histopathological grading by two independent pathologists and CD3/PAX5 marker analysis. Normal lymph node samples were obtained from canines that were euthanized for non-lymphoma conditions. Microarray data were generated from 35 canine samples (25 DLBCL and 10 healthy) in total. However, data from 2 canine DLBCL samples did not meet our required quality and were removed from further analysis. Only data from 33 (23 DLBCL and 10 healthy) samples were used for analysis. The generated data were used for differential expression analysis, co-expression analysis and pathway analysis, and compared with analysis of publicly available microarray data (GSE12195) from human healthy and DLBCL lymph nodes. The comparisons between species at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa.
2013-09-26 | E-GEOD-30881 | biostudies-arrayexpress
Project description:A databank of canine WGS data prepared by the AHT for cross-breed analysis
| PRJEB36030 | ENA
Project description:Background and objective: The role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been addressed. We previously demonstrated that DNA damage was found in bronchiole at early phase, and subsequently extended to alveolar cells at later phase in bleomycin-induced pulmonary fibrosis in mice. Club cells are progenitor cells for bronchiole, and are recognized to play protective roles against lung inflammation and damage. The aim of the study was to elucidate the role of club cells in the development of pulmonary fibrosis. Methods: C57BL/6J mice were received naphthalene intraperitoneally at day -2 to deplete club cells, and were given intratracheal bleomycin or vehicle at day 0. Lung tissues were obtained at day 1, 7, and 14, and bronchoalveolar lavage was performed at day 14. Gene expression was analysed from bronchiolar ephithelial cells sampled by laser captured microdissection at day 14. Results: Surprisingly, naphthalene-induced club cell depletion protected mice from bleomycin-induced lung injury and fibrosis. We conclude that club cells are involved in the development of lung injury and fibrosis.
2017-02-08 | GSE94522 | GEO