Neoadjuvant chemotherapy has been shown to be equivalent to post-operative treatment for breast cancer, and allows for assessment of chemotherapy response. In a pilot trial of docetaxel (T) and capecitabine (X) neoadjuvant chemotherapy for Stage II/III BC, we assessed correlation between baseline gene expression and tumor response to treatment, and examined changes in gene expression associated with treatment. Patients received 4 cycles of TX. Tumor tissue obtained from Mammotome core biopsies pretreatment (BL) and post-Cycle 1 (C1) of TX was flash frozen and stored at -70C until processing. Gene expression analysis utilized Affymetrix HG-U133 Plus 2.0 GeneChip arrays. Statistical analysis was performed using BRB Array Tools after RMA normalization. Gene ontology (GO) pathway analysis used random variance t-tests with a significance level of p<0.005. For gene categories identified by GO pathway analysis as significant, expression levels of individual genes within those pathways were compared between classes using univariate t-tests; those genes with significance level of p<0.05 were reported.
Gene expression pathway analysis to predict response to neoadjuvant docetaxel and capecitabine for breast cancer.
Specimen part, Time
View SamplesWe performed single-cell mRNA-Seq on wild-type mouse keratinocytes co-cultured with keratinocytes in which beta-catenin was activated. We identified seven distinct cell states in cultures that had not been exposed to the beta-catenin stimulus. Using temporal single-cell analysis we reconstruct the cell fate changes induced by neighbor Wnt activation. Gene expression heterogeneity was reduced in neighboring cells and this effect was most dramatic for protein synthesis associated genes. The changes in gene expression were accompanied by a shift from a quiescent to a more proliferative stem cell state. By integrating imaging and reconstructed sequential gene expression changes during the state transition we identified transcription factors, including Smad4 and Bcl3, that were responsible for effecting the transition in a contact-dependent manner. Our data indicate that non cell autonomous Wnt/beta-catenin signaling decreases transcriptional heterogeneity and further our understanding of how epidermal Wnt signaling orchestrates regeneration and self-renewal. Overall design: Comparison of cells exposed to Wnt activated neighbors versus unactivated.
Epidermal Wnt signalling regulates transcriptome heterogeneity and proliferative fate in neighbouring cells.
Specimen part, Treatment, Subject
View SamplesBackground: Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems. We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods: Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete Freunds adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results: Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions: These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression, demonstrating long-term effects of PAE on the CNS response under steady-state conditions and following an inflammatory insult. Key words: prenatal alcohol exposure (PAE), ethanol, inflammation, arthritis, gene expression, rat.
Prenatal alcohol exposure alters steady-state and activated gene expression in the adult rat brain.
Sex, Specimen part, Disease
View SamplesWe used two RNA-Seq methods to measure the the global transcription levels in mouse liver cells. The data here provide insight into the pros and cons of whole transcript method and 3' RNA-Seq method. Overall design: KAPA (whole transcript method) and Lexogen (3' RNA-Seq method) were used to compare global expression in 6 mice of two conditions: 1) 3 normal diet mice 2) 3 iron-loaded diet mice.
A comparison between whole transcript and 3' RNA sequencing methods using Kapa and Lexogen library preparation methods.
Sex, Age, Specimen part, Cell line, Subject
View SamplesBACKGROUND: Understanding individual patient host response to viruses is key to designing optimal personalized therapy. Unsurprisingly, in-vivo human experimentation to understand individualized dynamic response of the transcriptome to viruses are rarely studied because of the obvious limitations stemming from ethical considerations of the clinical risk.
Towards a PBMC "virogram assay" for precision medicine: Concordance between ex vivo and in vivo viral infection transcriptomes.
Specimen part, Subject
View SamplesWe sequenced liver mRNA from 23 individual pigs (5 prefed and 18 fasted) taken at 4 separate time points to evaluate the change in gene expression over the course of hemorrhagic shock and resuscitation in response to a carbohydrate prefed state. Overall design: Examination of mRNA levels in liver biopsies from pigs at 4 timepoints throughout hemorrhagic shock and resuscitation
Fed state prior to hemorrhagic shock and polytrauma in a porcine model results in altered liver transcriptomic response.
Specimen part, Cell line, Subject, Time
View SamplesPIP3 is synthesized by PI3Ks and regulates complex cell responses, such as growth and migration. Signals that drive long-term reshaping of cell phenotypes are difficult to resolve because of complex feedback networks that operate over extended times. It is clear PIP3-dependent modulation of mRNA accumulation is important in this process but is poorly understood. We have quantified the genome-wide mRNA-landscape of non-transformed, breast epithelium-derived MCF10a cells and its response to transient (EGF or PI3Ka-selective inhibitor) or chronic (isogenic cells expressing an oncomutant PI3Ka allele or lacking the PIP3-phosphatase /tumour-suppressor, PTEN) perturbations of PIP3.These results show that whilst many mRNAs are changed by long-term genetic perturbation of PIP3 signaling (“butterfly effect”), a much smaller number change with a directional logic that aligns with different PIP3 perturbations, allowing discrimination of more directly regulated mRNAs. Our results also indicate that mRNAs can be differentially sensitive to specific features of PIP3 signals, that PIP3-sensitive mRNAs encode PI3K pathway components and identify the transcription factor binding motifs SRF and PRDM1 as important regulators of PIP3-sensitive mRNAs involved in cell movement. Overall design: RNA-seq on WT MCF10a, treated or not with A66 (Pi3Kalpha inhibitor), PIK3CA H1047R MCF10a and PTEN KO MCF10a. EGF time course stimulation applied (0, 15, 40, 90, 180, 300 min). A66 no EGF when A66 was applied for 300min w/o EGF simulation. All samples made in triplicate. Total of 75 samples.
Perturbations of PIP3 signalling trigger a global remodelling of mRNA landscape and reveal a transcriptional feedback loop.
No sample metadata fields
View SamplesDuring animal development, signals determine and organize a vast number of complex tissues using a very small number of signal transduction pathways. These developmental signaling pathways determine cell fates through a coordinated transcriptional response that remains poorly understood. The Wnt pathway is involved in a variety of these cellular functions, and its signals are transmitted in part through a -catenin/TCF transcriptional complex. Here we report an in vivo Drosophila assay that we used to distinguish between activation, de-repression and repression of transcriptional responses, separating upstream and downstream pathway activation and canonical/non-canonical Wnt signals in embryos. We find a specific set of genes downstream of both -catenin and TCF with an additional group of genes regulated by Wnt. The non-canonical Wnt4 regulates a separate cohort of genes. We correlate transcriptional changes with phenotypic outcomes of cell differentiation and embryo size, showing our model can be used to characterize developmental signaling compartmentalization in vivo.
An embryonic system to assess direct and indirect Wnt transcriptional targets.
Specimen part
View SamplesAlthough hepatocyte-nuclear-factor-1 (Hnf1) is crucial for pancreas and liver functions, it is believed to play a limited functional role for intestinal epithelial functions. The aim of this study was to assess the consequences of abrogating Hnf1 on the maintenance of adult small intestinal epithelial functions.
Loss of hepatocyte-nuclear-factor-1alpha impacts on adult mouse intestinal epithelial cell growth and cell lineages differentiation.
Age, Specimen part, Disease
View SamplesTranscriptomes performed on left ventricular heart samples from mice of the hybrid mouse diversity panel, a set of over a hundred inbred strains of mice. In this project, the strains were challenged with Isoproterenol, a beta-adrenergic agonist to induce cardiac hypertrophy and failure. Results are useful for the analysis of heart-related traits in mice
Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.
Sex, Specimen part
View Samples