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SRP119838
Homo sapiens
24 Downloadable Samples
NextSeq 500
Description
BRAF oncogene is mutated in ~50% of human cutaneous melanomas. The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK) pathway fuelling cancer growth. The inhibitors of BRAF V600E (BRAFi), lead to massive and high response rate. However, BRAFi-resistant cells that operate as a cellular reservoir for relapses severely limits the duration of the clinical response. The recent depiction of these resistant cells did not identify druggable targets to ensure long-term survival under BRAFi. Here, we identify the aryl hydrocarbon receptor (AhR) as a target to eradicate resistant cells. We show that BRAFi bind to AhR on a new site, named beta-pocket, and reprogram gene expression independently of its partner ARNT. beta-pocket activation induces a pigmentation signature, which is associated to BRAFi-induced cell death of sensitive BRAF V600E melanoma cells and tumour shrinkage. Intriguingly, in resistant cells, BRAFi does not induced a pigmentation signature since these cells display another AhR program; AhR-ARNT dependant. By this way, AhR directs several key BRAFi-resistant genes. At single cell level, this constitutive activation of AhR-ARNT is identified in rare cells before BRAFi-treatment of melanoma tumours and an enrichment of these alpha-cells is observed under BRAFi. Our data strongly suggest that an endogenous AhR ligand activates AhR-ARNT via the canonical AhR pocket (alpha-pocket), thus favouring BRAFi-resistant gene expression. Importantly, we identify the clinically compatible AhR antagonist, the resveratrol (RSV), able to abrogate the deleterious constitutive activation of AhR and to reduce the cellular reservoir for the relapse. Taken together, this work reveals that constitutive AhR signalling drives BRAFi resistance and constitutes a therapeutic target to achieve long-term patient survival under BRAFi. More broadly, the constitutive activation of AhR by endogenous ligands is in line with the ability of UV radiations to generate potent AhR ligands and to favour melanoma onset. Overall design: Total RNA isolated from 12 human melanoma cell lines (501Mel) after different treatments was subjected to multiplexed RNA-sequencing using Illumina NextSeq500 sequencing tehnology.
Publication Title
Sustained activation of the Aryl hydrocarbon Receptor transcription factor promotes resistance to BRAF-inhibitors in melanoma.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
ZXDC1 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.
Publication Title
The zinc finger transcription factor ZXDC activates CCL2 gene expression by opposing BCL6-mediated repression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 293 Downloadable Samples
- Illumina HiSeq 2000
Description
In 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
Publication Title
Single-cell RNA-seq reveals dynamic, random monoallelic gene expression in mammalian cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
Neural 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
Publication Title
Laminar and dorsoventral molecular organization of the medial entorhinal cortex revealed by large-scale anatomical analysis of gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The 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.
Publication Title
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sequentially acting Sox transcription factors in neural lineage development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The 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.
Publication Title
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The 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.
Publication Title
Transcriptional shift identifies a set of genes driving breast cancer chemoresistance.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Danio rerio
- 6 Downloadable Samples
- IlluminaHiSeq2500
Description
We report changes in the levels of gene expression between 48hpf hearts and 56hpf hearts, the initial stages of valvulogenesis Overall design: 48hpf and 56hpf hearts were dissected and RNA was extracted. RNA profiles were then generated at each stage using Illumina deep sequencing
Publication Title
klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis.
Sample Metadata Fields
No sample metadata fields
View Samples