BRCA2A: We used microarrays to identify differentially expressed genes. We focused on those genes that were dramatically salicylic acid-induced (>2-fold) and BRCA2A-dependent in npr1 sni1 double mutants
Arabidopsis BRCA2 and RAD51 proteins are specifically involved in defense gene transcription during plant immune responses.
Specimen part, Treatment, Time
View SamplesWe used microarrays to identify differentially expressed genes after DNA-damaging agent bleomycin (BLM) and/or immune inducer 2, 6-dichloroisonicotinic acid (INA) treatment. We focused on those genes that were synergistically induced by co-treatment (BLM+INA).
Salicylic acid activates DNA damage responses to potentiate plant immunity.
Specimen part, Treatment
View SamplesWe sequenced mRNA from individual stormal cells (Macrophages, Monocytes, and Neutrophils) and tumor epithelial cells from KrasG12dD; p53-/- murine lung cancer model and WT control mouse to compare gene expressio profiles of lung cancer stroma and tumor cells to their counterparts of WT lugns. The tumor was generated by injecting HKP1 lung cancer cell line, which was driven by KrasG12D activation and loss of p53, via tail vein. The cells were sorted by their specific surface markers at day 20-25 after orthortopic lung cancer formation. Overall design: Examination of mRNA levels in individual stormal cells and tumor cells from tumor lungs compared to their counterparts from WT lungs
Transcriptome analysis of individual stromal cell populations identifies stroma-tumor crosstalk in mouse lung cancer model.
No sample metadata fields
View SamplesLung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC) as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor “activated/reprogrammed” stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM)-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils) identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN), chemokine (C-C motif) ligand 7 (CCL7) and thrombospondin 1 (TSP1) were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value. Overall design: We sorted pure populations of the immature monocytic myeloid cells (IMMCs), neutrophils (Neu), and epithelial cells (Epi) from tumors and adjacent lung tissues of stage I-III lung adenocarcinoma patients. RNA samples (totally 17 samples) were sequenced: from tumor IMMC (n=3), Neu (n=2), Epi (n=2); from adjacent lung IMMC (n=3), Neu (n=4), Epi (n=3).
Identification of Reprogrammed Myeloid Cell Transcriptomes in NSCLC.
No sample metadata fields
View SamplesLivers from 15 month old mice mainatined on one of 25 different diets varying in protein, carbohydrate, fat (P,C,F) and energy content were analysed. Energy content was categorised as low (8kJ/g), medium (13kJ/g) or high (17kJ/g) Mice were placed on diet from 3 weeks of age and a subset culled for various analyses. The rest of the cohort was allowed to live out their natural life to assess lifespan.
Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework.
Specimen part
View SamplesRecent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence of extended subpial grey matter lesions with significant neuronal/glial loss and microglial activation are associated with meningeal inflammation, including the presence of lymphoid-like structures in the subarachnoid space in a proportion of cases. To investigate the molecular consequences of pro-inflammatory and cytotoxic molecules diffusing from the meninges into the underlying grey matter, we carried out gene expression profiling analysis of the motor cortex from 20 post-mortem multiple sclerosis brains with and without substantial meningeal inflammation and 10 non-neurological controls. Gene expression profiling of grey matter lesions and normal appearing grey matter not only confirmed the substantial pathological cell changes, which were greatest in multiple sclerosis cases with increased meningeal inflammation, but also demonstrated the upregulation of multiple genes/pathways associated with the inflammatory response. In particular, genes involved in tumour necrosis factor (TNF) signalling were significantly deregulated in MS cases compared to controls.
Meningeal inflammation changes the balance of TNF signalling in cortical grey matter in multiple sclerosis.
Specimen part, Disease, Disease stage
View SamplesThe Collaborative Cross (CC) recombinant inbred panel was conceived as an ideal resource for mammalian system genetics. The pre-CC is a proof-of-concept experiment involving CC lines that have undergone at least five generations of inbreeding. Siblings from these lines were each involved in one of four distinct phenotyping arms, then genotyped on a high-density Affymetrix platform. The genetic profile of these emerging lines reveals high diversity, balanced allele frequencies, and well-distributed recombination all ideal qualities for a mapping panel. We have mapped white spot, a discrete trait; body weight, a highly polygenic complex trait; and more than 11,000 liver gene expression traits. These analyses provide a glimpse of the potential mapping power and resolution of the CC.
Genetic analysis of complex traits in the emerging Collaborative Cross.
Specimen part
View SamplesHematopoietic progenitor and stem cells from bone marrow have been sorted by FACS (LSK, Lineage -, Sca1 + and cKit +) and co-culture during 18h without cytokines with or without extracellular vesicles (EV) secreted by AFT stromal cells.
Extracellular vesicles of stromal origin target and support hematopoietic stem and progenitor cells.
Specimen part
View SamplesSelf-renewal and pluripotency in human embryonic stem cells (hESCs) depends upon the function of a remarkably small number of master transcription factors (TFs) that include OCT4, SOX2, and NANOG. Endogenous factors that regulate and maintain the expression of master TFs in hESCs remain largely unknown and/or uncharacterized. We use a genome-wide, proteomics approach to identify proteins associated with the OCT4 enhancer. We identify known OCT4 regulators, plus a subset of potential regulators including a zinc finger protein, ZNF207, that plays diverse roles during development. In hESCs, ZNF207 partners with master pluripotency TFs to govern self-renewal and pluripotency while simultaneously controlling commitment of cells towards ectoderm through direct regulation of neuronal TFs, including OTX2. The distinct roles of ZNF207 during differentiation occur via isoform switching. Thus, a distinct isoform of ZNF207 functions in hESCs at the nexus that balances pluripotency and differentiation to ectoderm. Overall design: examine gene expression changes in ZNF207 knock down hESCs
A distinct isoform of ZNF207 controls self-renewal and pluripotency of human embryonic stem cells.
Specimen part, Subject
View SamplesWe have identified a CD57+PD1- CD4 T cell phenotype at the time of transplantation that strongly correlates with subsequesnt development of belatacept-resistant rejection. In this study, we used microarray to determine which genes were upregulated in CD57+ compared to CD57- CD4 T cells.
CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.
Specimen part, Subject
View Samples