The role of post-transcriptional gene regulation in human brain development and cognitive diseases remains mostly uncharacterized. ELAV-like RNA binding proteins are a family of proteins that regulate several aspects of neuronal function including neuronal excitability and synaptic transmission. Here, we identify the downstream transcriptional networks of ELAVL2, an RNA-binding protein with unknown function in the brain. We knockdown expression of ELAVL2 in human neurons and conduct RNA-sequencing, identifying networks of differentially expressed and alternatively spliced genes with altered ELAVL2. These networks contain autism-relevant genes as well as previously identified targets of other RNA binding proteins implicated in autism spectrum disorders such as RBFOX1 and FMRP. ELAVL2-regulated coexpression networks are also enriched for synaptic genes as well as genes with human-specific patterns of gene expression in the frontal pole. Together, these data suggest that ELAVL2 regulation of transcript expression is critical for neuronal functions at risk in autism spectrum disorders and such mechanisms of post-transcriptional gene regulation may have contributed to human brain evolution. Overall design: We carried out RNA-sequencing (RNA-seq) of human neural progenitors cells. For the RNA-seq, 5 indipendent replicates were used for the neural progenitor cells. Primary human neural progenitor cultures were derived from mid-gestation fetal brain. Cells were transduced with a lentivirus containing a specific shRNA to ELAVL2 or a control shRNA. Cells were differentiated into neurons for 4 weeks and then harvested.
ELAVL2-regulated transcriptional and splicing networks in human neurons link neurodevelopment and autism.
No sample metadata fields
View SamplesIt has been shown previously that endothelial cells and LepR+ stromal cells are the main sources of SCF in vivo in the mouse bone marrow. We tested whether SCF from endothelial cells and/or LepR+ stromal cells is important for the maintenance of hematopoietic progenitors and erythroid progenitors in mouse bone marrow by conditional deletion of Scf from these two cell types. We discovered that Scf deletion from LepR+ stromal cells, but not endothelial cells, reduced the numbers of hematopoietic progenitors and erythroid progenitors in mice. We performed RNA-Seq on PreCFU-E and CFU-E progenitors from control mice and from mice with Scf deletion from LepR+ stromal cells. We discovered that lack of SCF from LepR+ cells induces a premature differentiation of PreCFU-E and CFU-E progenitors. Overall design: Examination of gene expression profile in 2 cell tyeps from 3 different genetic backgrounds
Restricted Hematopoietic Progenitors and Erythropoiesis Require SCF from Leptin Receptor+ Niche Cells in the Bone Marrow.
Sex, Specimen part, Subject
View SamplesOur findings demonstrate that CDCP1 is a novel modulator of HER2 signalling, and a biomarker for the stratification of breast cancer patients with poor prognosis
Interaction of CDCP1 with HER2 enhances HER2-driven tumorigenesis and promotes trastuzumab resistance in breast cancer.
Cell line
View SamplesBy utilizing mast cells lacking Dnmt3a, we found that this enzyme is involved in restraining mast cell responses to stimuli, both in vitro and in vivo.
<i>Dnmt3a</i> restrains mast cell inflammatory responses.
Sex, Specimen part, Treatment
View Samplesassess the efficacy of Pimasertib to characterize its mechanism of action
Combination of the MEK inhibitor pimasertib with BTK or PI3K-delta inhibitors is active in preclinical models of aggressive lymphomas.
Cell line, Treatment, Time
View SamplesBreast carcinoma (BC) have been extensively profiled by high-throughput technologies for over a decade, and broadly speaking, these studies can be grouped into those that seek to identify patient subtypes (studies of heterogeneity) or those that seek to identify gene signatures with prognostic or predictive capacity. The shear number of reported signatures has led to speculation that everything is prognostic in BC. Here we show that this ubiquity is an apparition caused by a poor understanding of the inter- relatedness between subtype and the molecular determinants of prognosis. Our approach constructively shows how to avoid confounding due to a patient's subtype, clinicopathological or treatment profile. The approach identifies patients who are predicted to have good outcome at time of diagnosis by all available clinical and molecular markers, but who experience a distant metastasis within five years. These inherently difficult patients (~7% of BC) are prioritized for investigations of intra-tumoral heterogeneity.
The prognostic ease and difficulty of invasive breast carcinoma.
Age, Disease stage, Time
View SamplesWe carried out RNA-sequencing (RNA-seq) of adult human postmortem neocortical brain tissue, and then correlated those expression values with the fMRI signal in each brain region Overall design: Ten cortical regions were included in the analysis: pre-motor cortex - PMV (BA6), dorsolateral prefrontal cortex – DLPFC (BA9), middle temporal gyrus – pMTG (BA21), superior temporal gyrus – pSTG (BA22), angular gyrus - AG (BA39), supramarginal gyrus - SMG (BA40), pars opercularis - POP (BA44), pars triangularis - PTr (BA45), middle frontal gyrus – MFG (BA46) and pars orbitalis - POrB (BA47). For each brain region, three or more samples from left adult brain hemispheres were collected (ages range from 33 to 49) and only males were included to avoid the effect of sex
Correspondence between Resting-State Activity and Brain Gene Expression.
No sample metadata fields
View SamplesIn the following experiment, three different hESC cell lines (HES2, MEL1 and H9) were grown in the presence of KOSR, KOSR or mTESR containing media respectively. KOSR (Knockout serum replacement medium) is a standard media allowing the growth of hESC without the need for manual passaging - Enzymatic passaging is used instread. mTESR (Ludwig et al., 2007) is a media allowing the growth of hESC on matrigel with enzymatic passaging. At day 7 after passaging, these cells were FACs sorted for the presence of GCTM-2 and CD9 into 4 distinct fractions (p4: GCTM-2-neg, CD9-neg; p5: GCTM-2-low, CD9-low; p6: GCTM-2-medium, CD9-medium and p7: GCTM-2-high, CD9-high). For each cell line-subfraction combination, RNA was harvested and subject to microarray.
Identification of human embryonic stem cell surface markers by combined membrane-polysome translation state array analysis and immunotranscriptional profiling.
No sample metadata fields
View SamplesExpression profiling of thymic lymphomas derived from HIF1a+/+, p53R270H/R270H; HIF1a+/-, p53R270H/R270H; and HIF1aKI/+, p53R270H/R270H mice.
Heterozygosity for hypoxia inducible factor 1alpha decreases the incidence of thymic lymphomas in a p53 mutant mouse model.
Age
View SamplesHES2 ESCs were grown in standard ES culture conditions. After 1 week, these cells were FACs sorted for the presence of GCTM-2 and CD9.
Identification of human embryonic stem cell surface markers by combined membrane-polysome translation state array analysis and immunotranscriptional profiling.
No sample metadata fields
View Samples