SF3B1, SRSF2 and U2AF1 are the most frequently mutated splicing factor genes in MDS. We have performed a comprehensive analysis to determine the impact of these commonly mutated splicing factors on pre-mRNA splicing in the stem/progenitor cells and in the erythroid and myeloid precursors in splicing factor mutant MDS. Using RNA-seq, we determined the aberrantly spliced genes and dysregulated pathways in bone marrow CD34+ cells of a large group of 82 MDS patients. Splicing factor mutations in MDS result in different mechanistic alterations in splicing and largely affect different genes, but these converged in common dysregulated pathways and cellular processes, including RNA splicing, translation and mitochondrial dysfunction, indicating that these mutations operate through common mechanisms in MDS. Many of these dysregulated pathways and cellular processes can be linked to the known disease pathophysiology and to the phenotypes associated with splicing factor mutations in MDS, whilst several others have not been previously associated with MDS, such as sirtuin signalling. Overall design: RNA-sequencing was performed on bone marrow CD34+ hematopoeitic stem and progenitor cells from patients with myelodysplastic syndrome and healthy controls to identify differential splicing between samples with mutations in the splicing factor SF3B1, SRSF2 or U2AF1 comparative to samples from myelodysplactic syndrome patients without mutations in these splicing factors and healthy controls. Processed data for the CD34+ hematopoeitic stem and progenitor cells are available in the files: CPM_table.txt.gz, Count_table.txt.gz and TPM_table.txt.gz. RNA-sequencing was also performed on monocytic, granulocytic and erythroid precursors from the bone marrow of patients with myelodysplastic syndrome and healthy controls to identify aberrant splicing in samples with mutations in splicing factors SF3B1 and SRSF2 comparative from healthy controls. Processed data for the monocytic, granulocytic and erythroid precursors are available in the files: CPM_table_fractions.txt, Count_table_fractions.txt and TPM_table_fractions.txt.
Impact of spliceosome mutations on RNA splicing in myelodysplasia: dysregulated genes/pathways and clinical associations.
Specimen part, Disease, Subject
View SamplesTo describe normal cardiac and brain development during late first and early second trimester in human fetuses using microarray and pathways analysis and the creation of a corresponding normal database. RNA from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST microarray chip. From the amassed data we investigated differences in cardiac and brain development within the 10-18 GA period dividing the sample by GA in three groups: 10-12 (H1), 13-15(H2) and 16-18(H3) weeks. A fold change of 2 or above adjusted for a false discovery rate of 5% was used as initial cut-off to determine differential gene expression for individual genes. Test for enrichment to identify functional groups were carried out using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly identified the cardiac specific genes, and transcripts reported to be differentially expressed were confirmed by qRT-PCR.
Metabolic gene profile in early human fetal heart development.
Specimen part
View SamplesBecause most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions.
Transcriptomics of post-stroke angiogenesis in the aged brain.
Sex, Age, Specimen part
View SamplesResponse of JHCO9 and JHOC5 cells to infection with NT (control) lentivirus or one of two knockdown lentiviruses, SPINK1 KD or IL-6 KD.
Targeting an autocrine IL-6-SPINK1 signaling axis to suppress metastatic spread in ovarian clear cell carcinoma.
Specimen part, Cell line
View SamplesCD69 is a transmembrane protein expressed on the surface of activated leukocyte. The ligand for CD69 and the intracellular signaling pathway of this molecule are yet unknown. It is widely used as a marker of activated lymphocyte, but its function in immune system is not known.
CD69 regulates type I IFN-induced tolerogenic signals to mucosal CD4 T cells that attenuate their colitogenic potential.
Specimen part
View SamplesDifferential gene expression between naive and activated CD8+ T cells was assessed using microarray analysis to determine target genes for new positron emission tomography (PET) probe screening, in particular for molecular imaging of lymphoid organs and immune activation.
Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2'-deoxycytidine analog.
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View SamplesUterine receptivity implies a dialogue between the hormonally primed maternal endometrium and the free-floating blastocyst. Endometrial stromal cells proliferate, avert apoptosis, and undergo decidualization in preparation for implantation; however, the molecular mechanisms that underlie differentiation into the decidual phenotype remain largely undefined. The Notch family of transmembrane receptors transduce extracellular signals responsible for cell survival, cell-to-cell communication, and trans-differentiation, all fundamental processes for decidualization and pregnancy. Using a murine artificial decidualization model, pharmacological inhibition of Notch signaling by gamma-secretase inhibition resulted in significantly decreased deciduoma. Furthermore, a progesterone receptor (PR)-Cre Notch1 bigenic (Notch1d/d) confirmed a Notch1-dependant hypomorphic decidual phenotype.
Notch1 mediates uterine stromal differentiation and is critical for complete decidualization in the mouse.
Sex, Age, Specimen part
View SamplesPancreas organogenesis is a highly dynamic process where neighbouring tissue interactions lead to dynamic changes in gene regulatory networks that orchestrates endocrine, exocrine and ductal lineage formation. To understand the spatio-temporal regulatory logic we have used the Forkhead transcription factor Foxa2-Venus fusion (FVF) knock-in reporter mouse to separate the FVF+ pancreatic epithelium from the FVF- surrounding mesenchyme and blood vessels to perform a whole genome-wide mRNA expression profiling at embryonic day (E)12.5-15.5. This allowed us to annotate genes and molecular processes differentially regulated in these cell types and compartments of the pancreas to generate a dynamic transcriptional landscape.
The global gene expression profile of the secondary transition during pancreatic development.
Specimen part
View SamplesWe sought to determine whether Ldh activity in SCC tumors is a marker of the cell type from which these cells arise, or a key metabolic activity important for tumor initiation or progression. Here we show that genetic abrogation of Ldh enzyme activity in HFSC-mediated tumorigenesis had no effect on tumor number, time to tumor formation, tumor proliferation, epithelial to mesenchymal transition in tumors, gene expression in tumors, tumor pathology, or the immune response to tumors. Overall design: Examination of mRNA profile of five LDHA knockout mice vs five wild type (WT) mice using Illumina HiSeq2500.
Increased lactate dehydrogenase activity is dispensable in squamous carcinoma cells of origin.
Specimen part, Subject
View SamplesResponse of pancreas cancer cells to treatment with recombinant MMP3
Tumor cell-derived MMP3 orchestrates Rac1b and tissue alterations that promote pancreatic adenocarcinoma.
Specimen part, Cell line, Treatment
View Samples