Uremic media calcification is not only driven by systemic factors such as hyperphosphatemia, but also crticially dependent on vascular smooth muscle cells per se. We hypothesized that the different developmental origins of vscular smooth muscle cells might lead to a heterogeneous susceptibility to develop media calcification.
Heterogeneous susceptibility for uraemic media calcification and concomitant inflammation within the arterial tree.
Specimen part
View SamplesAnalysis of gene expression on day four and day six after tumor inoculation.
Combined toll-like receptor 3/7/9 deficiency on host cells results in T-cell-dependent control of tumour growth.
Specimen part
View SamplesDeletions at 15q11.2 have been established to increase risk for multiple neurodevelopmental disorders (NDDs) including schizophrenia and epilepsy, yet show variable expressivity between individuals. To investigate the potential role of CYFIP1, a gene within the locus, we carried out knockdown experiments in human neural progenitor cells derived from 15q11.2 neutral induced pluripotent stem cells. Transcriptional profiling and cellular assays support a prominent role for CYFIP1 in cytoskeletal remodeling across all lines examined. Validating the utility of this model for study of disease, genes implicated in schizophrenia and epilepsy but not other disorders or traits unrelated to the deletion, were enriched among mRNAs dysregulated following knockdown. Importantly, and consistent with the variable expressivity of 15q11.2 deletions, the magnitude of disease-related effects varied between donor lines. Towards mechanisms, FMRP targets and synaptic genes were overrepresented among dysregulated mRNAs and as such may contribute to the schizophrenia and epilepsy effects we observe. Further model validation, and new candidate epilepsy genes, comes from machine-learning analyses showing a striking similarity between a subset of dysregulated transcripts and well-established epilepsy genes. Results provide support for an important contribution of CYFIP1 in 15q11.2 mediated risk for NDDs and demonstrate that disease-related biological signatures are evident prior to neuronal differentiation. This new human model of disease will be useful in identifying compounds that could ameliorate outcomes in deletion carriers. Overall design: Investigation of CYFIP1 shRNA knockdown in three neural progenitor cell lines derived from induced pluripotent stem cells (3 control samples and 3 knockdown samples analyzed in each line)
Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks.
No sample metadata fields
View SamplesWe report a new unsupervised clustering tool for single cell RNA-seq data called SC3. We show that biologically relevant information can be obtained from preneoplastic cells of patients with myeloprolifertive disease. Overall design: examination of three different patients with myeloproloferative disease
SC3: consensus clustering of single-cell RNA-seq data.
No sample metadata fields
View SamplesWe analysed the capacity of THP-1 cells (differentiated to macrophagoid cells) to recognize RNA sequences via pattern recognition receptors in vitro. Gene expression was analysed by RNA-Microarray. Cytokine production was analysed by ELISA assays.
Human TLR8 senses UR/URR motifs in bacterial and mitochondrial RNA.
Cell line, Treatment
View SamplesChronic lymphocytic leukemia (CLL) is a disorder of mature B cells. Most patients are characterized by indolent disease and an anergic phenotype of their leukemia cells which refers to a state of unresponsiveness to B cell receptor stimulation. Using the E-TCL1 mouse model, we show that B cell-specific ablation of NFAT2 leads to the loss of the anergic phenotype culminating in a significantly compromised life expectancy and histological transformation to aggressive disease. We further define a gene expression signature of anergic CLL cells consisting of several NFAT2-dependant genes employing microarray technology.
NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia.
Age, Specimen part
View SamplesJAK2 activation by TPO study and its downstream targets STAT1, STAT3 and STAT5 on Mouse HPC7 stem cells on four time points. The aim is to verify wether a JAK/STAT signalling signature is similar to the age-related functional decline in the haematopoietic system.
Proliferation Drives Aging-Related Functional Decline in a Subpopulation of the Hematopoietic Stem Cell Compartment.
Cell line, Treatment, Time
View SamplesBone marrow derived macrophages 1 M CpG or 20 g/ml TDB, an analogon to the mycobacterial cord factor TDM for 8h, 24h, 48h and 72h respectively.
Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation.
No sample metadata fields
View SamplesBone marrow derived macrophages from wt and card9 KO mice were stimulated with CpG, Curdlan or TDB, an analogon to the mycobacterial cord factor TDM for 48h, respectively.
Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRgamma-Syk-Card9-dependent innate immune activation.
No sample metadata fields
View SamplesAZD1208 is a novel PIM kinase inhibitor that we have shown inhibits tumorigenesis in tissue recombination models, Myc-CaP allograft models, and human prostate cancer xenografts. We sought to determine the intracellular pathways that are responsible for the anti-tumor effect. To this end we used the tissue recombination protocol to implant MYCCaP cells into castrated mice. MYCCaP cells are an androgen-dependent mouse cell line that overexpresses the oncogene MYC. The mice used for implantation were castrated, so any tumors that result from the grafting procedure are androgen-independent. The grafted mice were divided into a control population receiving vehicle, and a test population receiving AZD1208. The tumors were harvested and in vitro cell lines were made. The new cell lines have been perpetuated in androgen-depleted media.
PIM kinase inhibitor AZD1208 for treatment of MYC-driven prostate cancer.
Cell line
View Samples