The Wilms'' Tumour gene 1 (WT1), encodes for a complex protein with transcription factor activity which is essential in mammals throughout life. We provide a complete study of WT1 expression across different breast cancer subtypes as well as isoform specific expression analysis. Using in vitro cell lines, clinical samples and publicly available gene expression datasets, we demonstrate that WT1 plays a role in regulating the epithelial-mesenchymal balance of breast cancer cells and that WT1-expressing tumours are mainly associated with a mesenchymal phenotype. WT1 gene expression also correlates with CYP3A4 levels and is associated with poorer response to taxane treatment. Overall design: RNA profiles of breast cancer cells (MDA-MB-157) were generated by deep sequencing on the Illumina HiSeq 2000 platform. Untreated MDA-MB-157 cells, MDA-MB-157 cells transduced with a lacZ control vector, and MDA-MB-157 cells transduced with a lentiviral vector carrying a Wt1 shRNA were sequenced (titled untreated, lacZ and Wt1 respectively).
WT1 expression in breast cancer disrupts the epithelial/mesenchymal balance of tumour cells and correlates with the metabolic response to docetaxel.
No sample metadata fields
View SamplesThe PR domain containing 1a, with ZNF domain factor, gene prdm1a plays an integral role in the development of a number of different cell types during vertebrate embryogenesis, including neural crest cells, Rohon-Beard (RB) sensory neurons and the cranial neural crest-derived craniofacial skeletal elements. To better understand how Prdm1a regulates the development of various cell types in zebrafish, we performed a microarray analysis comparing wild type and prdm1a mutant embryos and identified a number of genes with altered expression in the absence of prdm1a. Rescue analysis determined that two of these, sox10 and islet1, lie downstream of Prdm1a in the development of neural crest cells and Rohon-Beard neurons, respectively. In addition, we identified a number of other novel downstream targets of Prdm1a that may be important for the development of diverse tissues during zebrafish embryogenesis.
prdm1a Regulates sox10 and islet1 in the development of neural crest and Rohon-Beard sensory neurons.
Age, Specimen part
View SamplesThe histone methyltransferase mixed lineage leukemia (MLL) is essential to maintain hematopoietic stem cells and is a leukemia protooncogene. Although Hox genes are well-characterized targets of MLL and MLL fusion oncoproteins, the range of Mll-regulated genes in normal hematopoietic cells remains unknown. Here we identify and characterize part of the Mll-transcriptional network in hematopoietic stem cells with an integrated approach by using conditional loss-of-function models, genomewide expression analyses, chromatin immunoprecipitation, and functional rescue assays. The Mll-dependent transcriptional network extends well beyond the previously appreciated Hox targets, is comprised of many characterized regulators of self-renewal, and contains target genes that are both dependent and independent of the MLL cofactor, Menin. Interestingly, Prdm16 emerged as a target gene that is uniquely effective at partially rescuing Mll-deficient hematopoietic stem and progenitor cells. This work highlights the tissue-specific nature of regulatory networks under the control of MLL/Trithorax family members and provides insight into the distinctions between the participation of MLL in normal hematopoiesis and in leukemia.
An MLL-dependent network sustains hematopoiesis.
Specimen part
View SamplesInnate immune cells control acute eosinophilic lung inflammation induced by cystein proteases. Here we characterize the dynamic change of gene expression profile in basophils, natural helper cells and eosinophils during lung inflammation via cystein protease Overall design: Examination of mRNA levels in individual cell populations, basophils, natural helper cells and eosinophils of the lung from naïve mice and papain treated mice.
Basophil-derived interleukin-4 controls the function of natural helper cells, a member of ILC2s, in lung inflammation.
No sample metadata fields
View SamplesRNA sequencing of ILC2s sorted from ß2 adrenergic receptor agonist-treated and non-treated mice Overall design: RNAs of ILC2s sorted as KLRG1+CD127+CD90+Lin-CD45+ from ß2 adrenergic receptor agonist-treated and non-treated mice mLNs 4 days post N. brasiliensis infection were analyzed
β<sub>2</sub>-adrenergic receptor-mediated negative regulation of group 2 innate lymphoid cell responses.
Specimen part, Cell line, Treatment, Subject
View SamplesAntibiotic-treated (ABX) mice exhibit an impaired innate and adaptive antiviral immune response and substantially delayed viral clearance following exposure to systemic LCMV or mucosal influenza virus. Genome-wide transcriptional profiling of macrophages isolated from ABX mice revealed decreased expression of genes associated with antiviral immunity. Moreover, macrophages from ABX mice exhibited defective responses to type I and type II IFNs and impaired capacity to limit viral replication. Collectively, these data indicate that commensal-derived signals provide tonic immune stimulation that establishes the activation threshold of the innate immune system required for optimal antiviral immunity.
Commensal bacteria calibrate the activation threshold of innate antiviral immunity.
Sex, Specimen part, Treatment
View SamplesDifference in RNA content of different cell types introduces bias to gene expression deconvolution methods. If ERCC spike-ins are introduced into samples, predicted proportions of deconvolution methods can be corrected Overall design: Two cell types of distinctly different sizes and RNA per cell content: HEK cells and Jurkat cells were mixed in different proportions ensuring that each mixture contained total of one million cells. We sequenced RNA of the samples (including ERCC spike-in controls to 382 be able to control for the absolute RNA-concentration).
Complete deconvolution of cellular mixtures based on linearity of transcriptional signatures.
Cell line, Subject
View SamplesWe provide a map of human ILC heterogeneity across multiple anatomical sites. Tissue-specific distinctions are particularly apparent for ILC1 populations, whose distribution was markedly altered in obesity or aging. Furthermore, the degree of ILC1 population hetero- geneity differed substantially in lymphoid versus mucosal sites. Together, these analyses comprise a comprehensive characterization of the spatial and temporal dynamics regulating the anatomical distri- bution, subset heterogeneity, and functional poten- tial of ILCs in non-diseased human tissues. Overall design: We present a quantitative analysis of ILC distribution and heterogeneity in lymphoid, mucosal, and metabolic tissues obtained from a diverse cohort of 44 previously non-diseased organ donors over a wide range of ages and body mass indexes (BMIs).
Spatial and Temporal Mapping of Human Innate Lymphoid Cells Reveals Elements of Tissue Specificity.
Specimen part, Subject
View SamplesHuman T-lymphotropic virus type 1 (HTLV-1) is associated with the development of Adult T-cell Leukemia, an aggressive CD4+ T-cells malignancy. Here, we have developed a new procedure to infect humanized mice with proviruses displaying specific mutations, such as one leading to the loss of the PDZ domain-binding motif (PBM) of Tax. In order to specifically analyze the in vivo role of the PBM of Tax, a comparative study of infected hu-mice was performed. We used next-generation sequencing to perform genome-wide transcriptomic analysis of T-cells infected with wild-type HTLV-1 virus or with virus bearing a mutated form of Tax lacking the PBM. Our results suggest that Tax PBM might be involved in the regulation of genes implicated in proliferation, apoptosis and cytoskeleton organization. Overall design: mRNA profiles of T-cells obtained from hu-Mice infected with wild-type or Tax-PBM HTLV-1 were generated by deep-sequencing in triplicates using Illumina's Hiseq3000 platform.
PDZ domain-binding motif of Tax sustains T-cell proliferation in HTLV-1-infected humanized mice.
Specimen part, Subject
View SamplesType 1 diabetes (T1D) is an autoimmune disease triggered by T cell reactivity to protein antigens produced by the -cells. Here we present a chronological compendium of transcriptional profiles from islets of Langerhans isolated from non-obese diabetic (NOD) mice ranging from 2 wks up to diabetes and compared to controls. Parallel analysis was made of cellular components of the islets. Myeloid cells populated the islets early during development in all mouse strains. This was followed by a type I interferon signature detectable at 4-6 wks of age only in diabetes susceptible mice. Concurrently, CD4 T cells were found within islets, many in contact with intra-islet antigen presenting cells. Early cellular signs of islet reactivity were detected by six wks. By 8 wks, NOD islets contained all major leukocytes populations and an inflammatory gene signature. This work establishes the natural transcriptional signature of T1D and provides a resource for future research.
Defining the transcriptional and cellular landscape of type 1 diabetes in the NOD mouse.
Specimen part
View Samples