Aberrant activation of -catenin is a common event in Acute Myeloid Leukemia (AML), and is recognized as an independent predictor of poor prognosis. Although increased -catenin signaling in AML has been associated with AML1-ETO and PML-RAR translocation products, and activating mutations in the FLT3 receptor, it remains unclear which mechanisms activate -catenin in AML more broadly. Here, we describe a novel link between interleukin-3 (IL-3) signaling and the regulation of -catenin in myeloid transformation and AML. Using a murine model of HoxB8 and IL-3 cooperation we show that IL-3 modulates -catenin protein levels, and Cre-induced deletion of -catenin abolishes IL-3 dependent growth and colony formation. In the erythroleukemic cell line TF-1.8, we observed increased -catenin protein levels and nuclear localization in response to IL-3, which correlated with transcriptional induction of -catenin target genes. Furthermore, IL-3 promoted -catenin accumulation in a subset of AML patient samples, and microarray gene expression analysis of these cells revealed induction of WNT/-catenin and TCF4 transcriptional gene signatures in an IL-3 dependent manner. This study is the first to link -catenin activation to IL-3 and suggests that targeting IL-3 signaling may be an effective approach for the inhibition of -catenin activity in some patients with AML.
Interleukin-3-mediated regulation of β-catenin in myeloid transformation and acute myeloid leukemia.
Specimen part, Disease, Treatment
View Samples14-3-3 proteins facilitate cytoplasmic-nuclear shuttling of transcription factors.Adipocyte differentiation requires the function of critical transcription factors to drive the development of a mature adipocyte. The aim of the study was to investigate if 14-3-3? is required for the adipogenic transcriptional program. Overall design: Examination of the transcriptome in siCon- and si14-3-3?-transfected 3T3-L1 cells undergoing differentiation at t=0, 24, and 48 hours.
14-3-3ζ coordinates adipogenesis of visceral fat.
No sample metadata fields
View SamplesDue to inherent differences in adipcoyte size between wildtype and knockout animals, we sought to examine if the decrease in adipocyte size was due to differences in the transcriptome and more specifcially, adipogenic genes. Overall design: Examination of the transcriptome in wildtype (WT) and knockout (KO) gonadal white adipose tissue from adult mice
14-3-3ζ coordinates adipogenesis of visceral fat.
No sample metadata fields
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 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