To gain insights into tumor heterogeneity in anti-cancer drug responses of patient-derived xenograft models of HER2+ breast cancer brain metastases, we performed transcriptome gene expression profiling by Ion AmpliSeqâ„¢ Transcriptome sequencing that targets more than 20,000 human genes. Our data found that all anti-cancer drugs responders have significantly higher expression levels of AKT-mTOR-dependent signature genes as compared to the non-responders, suggesting that most HER2+ breast cancer brain metastases are depend on the AKT-mTOR pathway Overall design: Gene expression profiles of five PDX samples were generated by Ion AmpliSeq Transcriptome sequencing, in duplcate, using Ion torrent Proton machine.
Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases.
Specimen part, Disease, Subject
View SamplesFoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis
FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis.
Cell line
View SamplesCombination therapy with Smo and PI3K inhibitors results in a synergistic effect in reducing tumor growth in PTEN-deficient Glioblastoma. To identify consequences of combination therapy with an Smo inhibitor and a PI3K inhibitor on a genome-wide scale, we performed Affymetrix microarrays with two different PTEN-deficient GBMs treated with single drugs or combination therapy. A small set of genes was significantly affected by combination therapy in hBT70 and/or hBT112, including several genes implicated in GBM prognosis, or identified as targets of Shh, PI3K or S6 pathways 29-33 .
Coordinate activation of Shh and PI3K signaling in PTEN-deficient glioblastoma: new therapeutic opportunities.
Treatment
View SamplesMutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-Hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2- hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the accumulation of D2-HG, we generated transgenic mice with conditionally activated IDH2R140Q and IDH2R172K alleles. Global induction of mutant IDH2 expression in adults resulted in dilated cardiomyopathy, white matter abnormalities throughout the central nervous system (CNS), and muscular dystrophy. Embryonic activation of mutant IDH2 resulted in more pronounced phenotypes, including runting, hydrocephalus, and shortened life spanrecapitulating the abnormalities observed in D2HGA patients. The diseased hearts exhibited mitochondrial damage and glycogen accumulation with a concordant upregulation of genes involved in glycogen biosynthesis. Notably, mild cardiac hypertrophy was also observed in nude mice implanted with IDH2R140Q expressing xenografts, suggesting that 2HG may potentially act in a paracrine fashion. Finally, we show that silencing of IDH2R140Q in mice with an inducible transgene restores heart function by lowering 2HG levels. Together, these findings indicate that inhibitors of mutant IDH2 may be beneficial in the treatment of D2HGA and suggest that 2HG produced by IDH mutant tumors has the potential to provoke a paraneoplastic condition.
D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice.
Specimen part
View SamplesZXDC1 augments the expression of various markers of monocyte/macrophage differentiation when over-expressed in the U937 cell line treated with the phorbol ester PMA. Likewise, knockdown of ZXDC1 restricts the induced expression of these markers. We sought to identify specfic gene targets of ZXDC1 during the process of monocyte/macrophage differentiation in U937 by performing gene expression profiling in cells exhibiting reduced expression of ZXDC1 compared to controls.
The zinc finger transcription factor ZXDC activates CCL2 gene expression by opposing BCL6-mediated repression.
Specimen part, Cell line
View SamplesIn the diploid genome, genes come in two copies, which can have different DNA sequence and where one is maternal and one is paternal. In a particular cell, a gene could potentially be expressed from both copies (biallelic expression) or only one (monoallelic). We performed RNA-Sequencing on individual cells, from zygote to the cells of the late blastocyst, and also individual cells from the adult liver. Using first generation crosses between two distantly related mouse strains, CAST/Ei and C57BL/6, we determined the expression separately from the maternal and paternal alleles. We found that half of the genes were expressed by only one allele, randomly so that some cells would express the paternal allele, some the maternal and a few cell both alleles. We also observed the spread of the progressive inactivation of the paternal X chromosome. Overall design: First generation mouse strain crosses were used to study monoallelic expression on the single cell level
Single-cell RNA-seq reveals dynamic, random monoallelic gene expression in mammalian cells.
No sample metadata fields
View SamplesNeural circuits in the medial entorhinal cortex (MEC) encode an animal’s position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations. Overall design: Examination of dorsal and ventral regions from 4 replicate samples each containing pooled data from 3-4 mice
Laminar and dorsoventral molecular organization of the medial entorhinal cortex revealed by large-scale anatomical analysis of gene expression.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sex, Age, Specimen part, Treatment
View SamplesThe aim of this study was to compare the gene expression profile changes breast tumors after the treatment with Anthracyclines and Taxanes. To this end, an oligonucleotide microarray was performed (Affymetrixs HG-U133 Plus 2.0 array). This gene expression study was carried out on the biopsied tumor samples previous being treated with chemotherapy, and subsequently compared with themselves once treatment schedule ended. The post-chemotherapy biopsy was obtained from the surgical piece. The goal of this study was the finding of several genes related to apoptosis, proliferation, differentiation, survival and transformation-related genes and correlating their differences in expression with the degree of response to chemotherapy, determined by the Miller and Payne histological grading system.
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sex, Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sequentially acting Sox transcription factors in neural lineage development.
Specimen part
View Samples