Here we used microarray expression profiling to characterise global changes in gene expression during stages of proliferation and differentiation of human neural stem cells
Associations of the Intellectual Disability Gene MYT1L with Helix-Loop-Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval.
Specimen part, Cell line
View SamplesKRAS mutations are present at a high frequency in human cancers. The development of therapies targeting mutated KRAS requires cellular and animal preclinical models. We exploited adeno-associated virus-mediated homologous recombination to insert the KRAS G12D allele in the genome of mouse somatic cells. Heterozygous mutant cells displayed a constitutively active Kras protein, marked morphologic changes, increased proliferation and motility but were not transformed. On the contrary, mouse cells in which we overexpressed the corresponding KRAS cDNA were readily transformed. The levels of Kras activation in knock-in cells were comparable with those present in human cancer cells carrying the corresponding mutation. KRAS-mutated cells were compared with their wild-type counterparts by gene expression profiling, leading to the definition of a "mutated KRAS-KI signature" of 345 genes. This signature was capable of classifying mouse and human cancers according to their KRAS mutational status, with an accuracy similar or better than published Ras signatures. The isogenic cells that we have developed recapitulate the oncogenic activation of Kras occurring in cancer and represent new models for studying Kras-mediated transformation. Our results have implications for the identification of human tumors in which the oncogenic KRAS transcriptional response is activated and suggest new strategies to build mouse models of tumor progression.
Knock-in of oncogenic Kras does not transform mouse somatic cells but triggers a transcriptional response that classifies human cancers.
No sample metadata fields
View SamplesTo uncover the chromosome 16 associated proteome and to take advantage of the generated knowledge to make progress in human biology in health and disease, a consortium of 15 groups was organized in four working groups: SRM and protein sequencing, antibody and peptide standard, clinical healthcare and biobanking and bioinformatics. According to a preliminary in silico study integrating knowledge from Ensembl, UniProt and GPM, Ramos B lymphocyte cells, MCF-7 epitelial cells and CCD18 fibroblast were selected as it is theoretically expected that any chromosome 16 protein coding gene is expressed in at least one of them. To define in detail the transcriptome of the above mentioned cell lines Affymetrix microarray based analyses were performed. Upon hybridization in Human ST 1.0 arrays, raw data were processed with RMA algorithm for background correction and normalization. Chromosome 16 gene expression pattern was then defined in each cell line and comparative analysis was done with R package statistics. Biological functions involving chromosome 16 genes were analysed with GO and functional networks were studied with Ingenuity Pathway Analysis. Expressed genes were compared with data from shotgun proteomic experiments to find the degree of correlation mRNA-protein. Expression of genes coding for proteins with weak or none MS evidence is shown. The integration of this information in decision-making process of the mass spectrometry group is discussed.
Spanish human proteome project: dissection of chromosome 16.
Cell line
View SamplesThis work studies the impact of AtNIGT1/HRS1-GR entrance in the nucleus upon DEX treatment in protoplasts.
AtNIGT1/HRS1 integrates nitrate and phosphate signals at the Arabidopsis root tip.
No sample metadata fields
View SamplesWe report that WT1 transcriptional repressor protein BASP1 interacts with oestrogen receptor alpha (Era), and interaction which in enhanced in the presence of Tamoxifen. We utilised RNASeq to identify common BASP1 and ERa target genes as well as Tamoxifen responsive genes that are altered in the absence of BASP1. Overall design: Total mRNA sequencing analysis of MCF7 cells treated with either siRNA against BASP1 or negative control siRNA, with and without Tamoxifen treatment. Each experiment was performed in triplicate.
BASP1 interacts with oestrogen receptor α and modifies the tamoxifen response.
No sample metadata fields
View SamplesThe aim was to investigate the effect of postoperative intra-abdominal infection on the gene expression patterns of peripheral blood leukocytes (PBL) after surgery for colorectal cancer
Peripheral blood leucocytes show differential expression of tumour progression-related genes in colorectal cancer patients who have a postoperative intra-abdominal infection: a prospective matched cohort study.
Specimen part, Disease, Disease stage
View SamplesStrategies to enhance islet b-cell survival and regeneration while refraining inflammation through manipulation of molecular targets would provide means to stably replenish the deteriorating functional b-cell mass detected in both Type 1 and Type 2 Diabetes Mellitus (T1DM and T2DM). Herein we report that over expression of the islet enriched transcription factor Pax4 refrains development of hyperglycemia in the RIP-B7.1 mouse model of T1DM through reduced insulitis, decreased b-cell apoptosis correlating with diminished DNA damage and increased proliferation. Transcriptomics revealed up regulation of genes involved in immunomodulation, cell cycle and ER homeostasis in islets over expressing Pax4 as compared to the T2DM-linked mutant variant Pax4R129W. Pax4 but not Pax4R129W protected islets from thapsigargin-mediated ER-stress apoptosis. Collectively, Pax4 is a critical signaling hub coordinating regulation of distinct molecular pathways resulting in improved b-cell fitness whereas Pax4R129W sensitizes to death under stress. More importantly we highlight potential common pharmacological targets for the treatment of DM.
PAX4 preserves endoplasmic reticulum integrity preventing beta cell degeneration in a mouse model of type 1 diabetes mellitus.
Age, Specimen part, Treatment
View SamplesLeft ventricular noncompaction (LVNC) Causes prominent ventricular trabeculations and reduces cardiac systolic function. The clinical presentation of LVNC ranges from asymptomatic to heart failure. We show that germline mutations in human MIB1 (mindbomb homolog 1), which encodes an E3 ubiquitin ligase that promotes endocytosis of the NOTCH ligands DELTA and JAGGED, cause LVNC in autosomal-dominant pedigrees, with affected individuals showing reduced NOTCH1 activity and reduced expression of target genes. Functional studies in cells and zebrafish embryos and in silico modeling indicate that MIB1 functions as a dimer, which is disrupted by the human mutations. Targeted inactivation of Mib1 in mouse myocardium causes LVNC, a phenotype mimicked by inactivation of myocardial Jagged1 or endocardial Notch1. Myocardial Mib1 mutants show reduced ventricular Notch1 activity, expansion of compact myocardium to proliferative, immature trabeculae and abnormal expression of cardiac development and disease genes. These results implicate NOTCH signaling in LVNC and indicate that MIB1 mutations arrest chamber myocardium development, preventing trabecular maturation and compaction. Overall design: RNA was isolated from the ventricles of 16 WT and 16 Mib1flox; CTnT-cre hearts at E14.5 and then pooled into four replicates.
Mutations in the NOTCH pathway regulator MIB1 cause left ventricular noncompaction cardiomyopathy.
No sample metadata fields
View SamplesSorting U2OS and HeLa cells genetically modified with the Fucci System allowed us to separate cells according to cell cycle progression followed by RNA Sequencing to characterize the oscillating transcriptome in cells without the need for chemical synchronization. Overall design: HeLa cells were sorted at three timepoints, while U2OS cells were sorted at two timepoints. Each time into three groups, categorized as "G1", "S", and "G2".
Comparative cell cycle transcriptomics reveals synchronization of developmental transcription factor networks in cancer cells.
Cell line, Subject
View SamplesWe used microarrays to detail genome-wide gene expression underlying cardiac myocyte pathologies and identified candidate genes and specific pathways affecting cardiac myopathies
Reduced phosphoinositide 3-kinase (p110alpha) activation increases the susceptibility to atrial fibrillation.
No sample metadata fields
View Samples