There is growing evidence that transplantation of cadaveric human islets is an effective therapy for type 1 diabetes. However, gauging the suitability of islet samples for clinical use remains a challenge. We hypothesized that islet quality is reflected in the expression of specific genes. Therefore, gene expression in 59 human islet preparations was analyzed and correlated with diabetes reversal after transplantation in diabetic mice. Analysis yielded 262 differentially expressed probesets, which together predict islet quality with 83% accuracy. Pathway analysis revealed that failing islet preparations activated inflammatory pathways, while functional islets showed increased regeneration pathway gene expression. Gene expression associated with apoptosis and oxygen consumption showed little overlap with each other or with the 262 probeset classifier, indicating that the three tests are measuring different aspects of islet cell biology. A subset of 36 probesets surpassed the predictive accuracy of the entire set for reversal of diabetes, and was further reduced by logistic regression to sets of 14 and 5 without losing accuracy. These genes were further validated with an independent cohort of 16 samples. We believe this limited number of gene classifiers in combination with other tests may provide complementary verification of islet quality prior to their clinical use.
Gene expression signature predicts human islet integrity and transplant functionality in diabetic mice.
Specimen part
View SamplesExperiment: Establishment of expression profiles in a brain metastasis from a PTC (RNA processing and hybridization to Affymetrix microarray done twice to yield a technical replicate), in non-brain metastatic, stage III and IV PTCs, and primary brain tumors. Biostatistics analysis identified genes and biofunctions related to the brain metastatic PTC.
Microarray expression profiling identifies genes, including cytokines, and biofunctions, as diapedesis, associated with a brain metastasis from a papillary thyroid carcinoma.
Sex, Disease stage
View SamplesNeuronal migration defects (NMDs) are among the most common and severe brain abnormalities in humans. Lack of disease models in mice or in human cells has hampered the identification of underlying mechanisms. From patients with severe NMDs we generated iPSCs then differentiated neural progenitor cells (NPCs). On artificial extracellular matrix, patient-derived neuronal cells showed defective migration and impaired neurite outgrowth. From a cohort of 107 families with NMDs, sequencing identified two homozygous C-terminal truncating mutations in CTNNA2, encoding aN-catenin, one of three paralogues of the a-catenin family, involved in epithelial integrity and cell polarity. Patient-derived or CRISPR-targeted CTNNA2- mutant neuronal cells showed defective migration and neurite stability. Recombinant aN-catenin was sufficient to bundle purified actin and to suppress the actin-branching activity of ARP2/3. Small molecule inhibitors of ARP2/3 rescued the CTNNA2 neurite defect. Thus, disease modeling in human cells could be used to understand NMD pathogenesis and develop treatments for associated disorders. Overall design: 2 biological replicates per individual (2 iPSC clone differentiations), excluding 1263A, which has one sample
Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.
No sample metadata fields
View SamplesExperiment: Establishment of expression profiles in HT, PTC with HT, PTC without HT, and mPTC in comparison to TN samples. TN samples were downloaded as CEL files from the repository of the microarray vendor. Biostatistical analysis focussed in first instance on identifying genes and biofunctions related to HT and PTC with HT.
Genetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis.
Sex, Disease
View SamplesPlants respond to environmental stresses by altering transcription of genes involved in the response. The chromatin modifier ATX1 influences gene expression and factors that modulate ATX1 activity would affect indirectly the expression of ATX1-regulated genes. Here, we demonstrate that dehydration is such a factor indicating that ATX1 is involved in the plants response to drought. In addition, we show that a hitherto unknown Arabidopsis gene, At3g10550, encodes MYO1, a phosphoinositide 3-phosphatase related to the animal myotubularins. By a functional genomics approach, we show that ATX1 and MYO1 participate in overlapping drought-response pathways. The shared set of genes, representing the ultimate targets of an ATX1-MYO1 signaling mechanism responding to drought, provided insights into the relationship of the epigenetic factor and the lipid phosphatase from the other end of the response pathway.
The Arabidopsis chromatin modifier ATX1, the myotubularin-like AtMTM and the response to drought.
No sample metadata fields
View SamplesIn order to identify potential genes that may play an important role in progression of colorectal carcinoma, we screened and validated the global gene expression using cDNA expression array on 36 CRC tissues and compared with 24 non-cancerous colorectal tissue.
Genome-wide expression analysis of Middle Eastern colorectal cancer reveals FOXM1 as a novel target for cancer therapy.
Sex
View SamplesExperiment: Expression profiling in breast cancer brain metastases (BC) compared to breast cancers (BC) and primary brain tumors (prBT). The objectives are to identify expression profiles that are specific to BCBM in order to identify new molecular biomarkers. The characterization of the BCBM samples included adjacent genetic techniques.
Comprehensive molecular biomarker identification in breast cancer brain metastases.
Sex, Specimen part, Disease stage
View SamplesTF1a AML cell line was selected for in vitro modelling of dormancy in AML. TF1-a were subjected to AML-niche-mimicking in vitro conditioning by culture with TGFB1 and the mTOR inhibitor rapamycin. Also TF1a cells were in vitro cultured with prolonged sublethal doses of Etoposide.
A molecular signature of dormancy in CD34<sup>+</sup>CD38<sup>-</sup> acute myeloid leukaemia cells.
Specimen part
View SamplesCumulus cells are biologically distinct from other follicular cells and perform specialized roles, transmitting signals within the ovary and supporting oocyte maturation during follicular development. The bi-directional communication between the oocyte and the surrounding cumulus cells is crucial for the acquisition of oocyte competence. Using Illumina/deep-sequencing technology, we dissected the small RNAome of pooled human mature MII oocytes and cumulus cells. Overall design: Cumulus cells and MII mature oocytes small RNA profiles were generated by deep-sequencing, using Illumina 1G sequencer
MicroRNAs: new candidates for the regulation of the human cumulus-oocyte complex.
Specimen part, Subject
View SamplesWe recently reported that carbon monoxide (CO) has bactericidal activity. To understand its mode of action we analysed the gene expression changes occurring when Escherichia coli, grown aerobically and anaerobically, is treated with the carbon monoxide releasing molecule, CORM-2. The E. coli microarray analysis shows that E. coli CORM-2 response is multifaceted with a high number of differentially regulated genes spread through several functional categories, namely genes involved in inorganic ion transport and metabolism, regulators, and genes implicated in posttranslational modification, such as chaperones. CORM-2 has higher impact in E. coli cells grown anaerobically, as judged by the existence of repressed genes belonging to eight functional classes which are absent in aerobically CORM-2 treated cells. In spite of the relatively stable nature of the CO molecule, our results show that CO is able to trigger a significant alteration in the transcriptome of E. coli which necessarily has effects in several key metabolic pathways.
Exploring the antimicrobial action of a carbon monoxide-releasing compound through whole-genome transcription profiling of Escherichia coli.
No sample metadata fields
View Samples