The complexity of the mature adult brain is a result of both developmental processes and experience-dependent circuit formation. One way to look at the process of brain development is to examine gene expression changes, and previous studies have used microarrays to address this in a global manner. However, the transcriptome is more complex than gene expression levels alone, as both alternative splicing and RNA editing occur to generate a more diverse set of mature transcripts. The aim of the current study was to develop a high-resolution transcriptome dataset of mouse cortical development using RNA sequencing (RNA-Seq), thus assaying exon usage and RNA editing as well as overcoming some of the inherent limitations of microarrays. We found a large number of differentially expressed genes, but also altered splicing and RNA editing between embryonic and adult cerebral cortex. Each dataset was validated both technically and biologically, and in each case tested we found our RNA-Seq observations to have high predictive validity. We propose this dataset, and the accompanying analysis, to be a helpful resource in the understanding of changes in gene expression during development. Overall design: Three young adult cerebral cortices four embryonic cerebral cortices
mRNA expression, splicing and editing in the embryonic and adult mouse cerebral cortex.
Specimen part, Cell line, Subject
View SamplesAlveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression of the PAX3-FOXO1 fusion gene. Despite its discovery over almost 20 years ago, PAX3-FOXO1 remains an enigmatic tumor driver. Previously, we reported that PAX3-FOXO1 supports aRMS initiation by enabling bypass of cellular senescence. Here, we show that bypass occurs in part by PAX3-FOXO1-mediated upregulation of RASSF4, a Ras-association domain family (RASSF) member, which then suppresses the evolutionarily conserved mammalian Hippo/Mst1 pathway. RASSF4 loss-of-function activates Hippo/Mst1 and inhibits downstream YAP, causing aRMS cell cycle arrest and senescence. This is the first evidence for an oncogenic role for RASSF4, and a novel mechanism for Hippo signaling suppression in human cancer.
Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression.
Cell line, Treatment
View SamplesTranscripomic analysis of leaf gene expression in S and N-deficient winter wheat during grain development. Tissue was harvested at anthesis and 7, 14 and 21 days post anthesis from experimental field plots.
Co-ordinated expression of amino acid metabolism in response to N and S deficiency during wheat grain filling.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesMutations in GRIN2B are associated with intellectual disability in humans. We generated iPSC derived mature cortical neurons with mutations in GRIN2B and compared them to isogenic control cells. We found that both loss of function (LOF) and reduced dosage (RD) mutations in GRIN2B lead to reduced expression of NMDAR genes and increased expression of marker of immaturity, including KI67 and MET. Overall design: Examination of transcriptome in iPSC-derved mature neurons with and without the presence of mutations in GRIN2B
Disruption of GRIN2B Impairs Differentiation in Human Neurons.
Subject
View SamplesTo probe the tissue source (cancer cell VS stromal cell) of gene expression in the mixed tumor samples, we took advantage of a set of Urothelial Cancer patient-derived xenograft (PDX) models given that the transcriptome in these models is a mixture of human RNA (derived from cancer cells) and mouse RNA (derived from stromal cells). Overall design: The cohort includes 5 different patient-derived PDX models, 3 replicates for each model, and thus a total of 15 samples
EMT- and stroma-related gene expression and resistance to PD-1 blockade in urothelial cancer.
Subject
View SamplesTo identify novel LXR target genes, we conducted transcriptional profiling studies using RAW264.7 cells ectopically expressing
Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR.
Cell line
View SamplesThe transcription factor GATA2 regulates chemotherapy resistance in prostate cancer. We report a novel GATA2 transcriptional program that has implications for chemotherapy resistance disease and aggressiveness in castration resistant prostate cancer. Overall design: Examination of the transcriptional network changes induced in human Ch-CRPC cell lines by two shRNA mediated knock down of GATA2 versus random shRNA control
A targetable GATA2-IGF2 axis confers aggressiveness in lethal prostate cancer.
No sample metadata fields
View SamplesMolecular mechanisms controlling specification and differentiation of distinct neuron subtypes in the cerebral cortex are not well understood. Corticothalamic projection neurons (CThPN) are a diverse set of neurons, critical for function of the neocortex, but little is known about the molecular mechansims controlling their development.
Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity.
Specimen part
View SamplesNFX1-91, a novel E6 cellular downstream target, functions as a transcriptional regulator and is involved in repressing hTERT expression. Other functions and downstream targets regulated by NFX1-91 were not well understood. We used microarrays to determine gene expression deregulated when NFX1-91 was knocked down.
NFX1 plays a role in human papillomavirus type 16 E6 activation of NFkappaB activity.
Cell line
View SamplesIn the past three years the role of inflammatory cytokines and chemokines in tumour promotion and progression has been intensively studied. The chemokine receptor CXCR4 and its ligand CXCL12 are commonly expressed in malignant cells from primary tumours, metastases and also in malignant cell lines. To investigate the biological significance of this receptor/ligand pair, we knocked-down CXCR4 expression in ovarian cancer cell line IGROV-1 using shRNA, and established stable cell lines.
A dynamic inflammatory cytokine network in the human ovarian cancer microenvironment.
No sample metadata fields
View Samples