The Notch signaling pathway controls cell fates through interactions between neighboring cells by positively or negatively affecting, in a context-dependent manner, processes of proliferation, differentiation, and apoptosis1. It has been implicated in human cancer both as an oncogene and a tumor suppressor2. Here we report, for the first time, novel inactivating mutations in the Notch pathway components in over forty percent of the human bladder cancers examined. Bladder cancer is the fourth most commonly diagnosed malignancy in the US male population3. Thus far, driver mutations in the FGFR3 and less commonly RAS proteins have been identified4,5. We show that Notch activation in bladder cancer cells suppresses proliferation both in vitro and in vivo by directly upregulating dual specificity phosphatases (DUSPs), thus reducing ERK1/2 phosphorylation. In mouse models, genetic inactivation of Notch signaling leads to ERK1/2 phosphorylation resulting in tumorigenesis in the urinary tract. In recent years, the tumor suppressor role of Notch has been recognized by loss-of-function mutations identified in myeloid cancers6 as well as squamous cell carcinomas of the skin, lung7, and the head and neck8,9. Of the 4 Notch receptors (N1-4), only N1 and 2 have been implicated in human cancer.
A new tumor suppressor role for the Notch pathway in bladder cancer.
Specimen part
View SamplesWe investigated the effects of a single pulse of growth hormone on the transcriptional activation of STAT5 target genes in hypophysectomized male mouse liver. This GEO series is part of a larger study, where we investigated the impact of a single pulse of GH given to hypophysectomized mice on local liver chromatin accessibility [DNase hypersensitive site analysis], transcription rates [hnRNA analysis], and gene expression [quantitative PCR and RNA-Seq] determined 30, 90 or 240 min later. The STAT5-dependent but sex-independent early GH response genes Igf1 and Cish showed rapid, GH pulse-induced increases in chromatin accessibility and gene transcription, reversing the effects of hypophysectomy. Rapid increases in liver chromatin accessibility and transcriptional activity were also induced in hypophysectomized male mice for some (Ces2b, Ugt2b38) but not for other liver STAT5-dependent male-biased genes (Cyp7b1). Moreover, in pituitary-intact male mice, Igf1, Cish, Ces2b and Ugt2b38 all showed remarkable cycles of chromatin opening and closing, and associated cycles of induced gene transcription, which closely followed each endogenous pulse of liver STAT5 activity. Thus, the endogenous rhythms of male plasma GH pulsation dynamically open and then close liver chromatin at discrete, localized regulatory sites in temporal association with transcriptional activation of Igf1, Cish and a subset of STAT5-dependent male-biased genes. Overall design: Liver RNA was isolated from hypophysectomized male mice that were untreated, or were treated with a single pulse of GH and euthanized 30, 90 or 240 minutes later. 8 Individual RNA samples were pooled to make 2 biological replicates per condition for RNA-seq analysis.
Activation of Male Liver Chromatin Accessibility and STAT5-Dependent Gene Transcription by Plasma Growth Hormone Pulses.
Sex, Age, Specimen part, Cell line, Treatment, Subject
View SamplesWe investigated the effects of a single pulse of growth hormone on the transcriptional activation of STAT5 target genes in hypophysectomized male mouse liver. This GEO series is part of a larger study, where we investigated the impact of a single pulse of GH given to hypophysectomized mice on local liver chromatin accessibility [DNase hypersensitive site analysis], transcription rates [hnRNA analysis], and gene expression [quantitative PCR and RNA-Seq] determined 30, 90 or 240 min later. The STAT5-dependent but sex-independent early GH response genes Igf1 and Cish showed rapid, GH pulse-induced increases in chromatin accessibility and gene transcription, reversing the effects of hypophysectomy. Rapid increases in liver chromatin accessibility and transcriptional activity were also induced in hypophysectomized male mice for some (Ces2b, Ugt2b38) but not for other liver STAT5-dependent male-biased genes (Cyp7b1). Moreover, in pituitary-intact male mice, Igf1, Cish, Ces2b and Ugt2b38 all showed remarkable cycles of chromatin opening and closing, and associated cycles of induced gene transcription, which closely followed each endogenous pulse of liver STAT5 activity. Thus, the endogenous rhythms of male plasma GH pulsation dynamically open and then close liver chromatin at discrete, localized regulatory sites in temporal association with transcriptional activation of Igf1, Cish and a subset of STAT5-dependent male-biased genes. Overall design: Liver RNA was isolated from untreated hypophysectomized male mice and from hypophysectomized male mice treated with a single pulse of GH and euthanized 30, 90 or 240 minutes later. 8 Individual RNA samples were pooled to make 2 biological replicates per condition for RNA-seq analysis.
Activation of Male Liver Chromatin Accessibility and STAT5-Dependent Gene Transcription by Plasma Growth Hormone Pulses.
Sex, Age, Specimen part, Cell line, Treatment, Subject
View SamplesAfter-ripening induced seed dormancy release in wheat is associated with mRNA oxidation.
Integrated analysis of seed proteome and mRNA oxidation reveals distinct post-transcriptional features regulating dormancy in wheat (Triticum aestivum L.).
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 SamplesAE9aId1fl/flCreER cells treated with the control vehicle, CBD or 4-OHT Overall design: We treated AE9aId1fl/flCreER leukemia with 0.1 µM 4-hydroxytamoxifen (4-OHT) for 48 hours or the Id1 inhibitor CBD (at 15 µM) for 16 hours, and isolated RNA for RNA-seq analysis.
Regulation of AKT signaling by Id1 controls t(8;21) leukemia initiation and progression.
No sample metadata fields
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 Samples