Using a chromatin regulator-focused shRNA library, we found that suppression of sex determining region Y-box 10 (SOX10) in melanoma causes resistance to BRAF and MEK inhibitors. To investigate how SOX10 loss leads to drug resistance, we performed transcriptome sequencing (RNAseq) of both parental A375 (Ctrl. PLKO) and A375-SOX10KD (shSOX10-1, shSOX10-2) cells. To ask directly whether SOX10 is involved indrug resistance in BRAF(V600E) melanoma patients, we isolated RNA from paired biopsies from melanoma patients (pre- and post- treatment) , that had gained BRAF or MEK inhibitor resistance . We performed RNAseq analysis to determine changes in transcriptome upon drug resistance. Overall design: Investigate genes regulated by SOX10 and differntial gene expression between pre- and post-treatment biopsies. We use short hairpin RNA to suppression SOX10 in A375 cells and cells were harvested with trizol reagent for RNA isolation. For paired biopsies (patient samples) we collected the first biopsy before the initiation of treatment and the second biopsy after drug resistance developed. RNA was isolated from FFPE samples and subjected for RNA sequencing.
Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma.
Sex, Age, Specimen part, Cell line, Subject
View SamplesBackground and Aim: Fra-1 (Fos-related antigen-1) is a member of the AP1 (activator protein-1) family of transcription factors. We have recently shown that Fra-1 is necessary for breast cancer cells to metastasize in vivo, and that breast cancer outcome can be predicted by a classifier comprising genes that are expressed in a Fra-1-dependent fashion. Here, we show that Fra-1 plays an important role also in colon cancer progression. Methods: We compared proliferation rates of parental and Fra-1-depleted colon cancer cells in vitro under 2D, 3D, and attachment-free conditions and in vivo upon subcutaneous and intravenous injections into mice. We also compared RNA expression profiles of colon cancer cells with and without Fra-1 expression. Results: Fra-1 depletion impair colony outgrowth of human colon cancer cells in soft agar and in suspension, whereas it does not affect proliferation on 2D culture plates. Consistent with this, upon subcutaneous injection into mice, tumors formed by Fra-1-depleted colon cancer cells are only three times smaller than those produced by control cells. In contrast, when injected intravenously, Fra-1 depletion causes 200-fold reduction in tumor burden. Consistent with the more aggressive characteristics of Fra-1-proficient tumors, the prognosis of colon cancer patients can be predicted by a Fra-1 classifier generated by comparing RNA profiles of parental and Fra-1-depleted colon cancer cells. Conclusions: Our results demonstrate that Fra-1 is an important determinant of the metastatic potential of human colon cancer cells, and suggest that a Fra-1 classifier can be used as a prognostic predictor in colon cancer patients. Overall design: HT29 cell line, two shRNAs against Fra-1, one empty vector control, three biological replicates
Fra-1 is a key driver of colon cancer metastasis and a Fra-1 classifier predicts disease-free survival.
No sample metadata fields
View SamplesClinicians need additional metrics for predicting quality of human oocytes for IVF procedures. Human polar bodies reflect the oocyte transcript profile. Quantitation of polar body mRNAs could allow for both oocyte ranking and embryo preferences in IVF applications. The transcriptome of a polar body has never been reported, in any organism. Overall design: Eight total samples. There are 2 biological replicates of the following four conditions: pooled oocytes and their sister polar bodies and a single oocyte and its sister polar body.
The transcriptome of a human polar body accurately reflects its sibling oocyte.
Specimen part, Subject
View SamplesNon-neuronal cell types such as astrocytes can contribute to Parkinson's disease (PD) pathology. The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is one of the most common known causes of familial PD. To characterize its effect on astrocytes, we developed a protocol to produce midbrain-patterned astrocytes from human induced pluripotent stem cells (iPSCs) derived from PD LRRK2 G2019S patients and healthy controls. In order to understand the effect of this mutation on astrocyte function, we compared the gene expression profiles of iPSC-derived midbrain-patterned astrocytes from PD patients with those from healthy controls. Overall design: Bulk RNA-Seq profiles of human iPSC-derived midbrain-patterned astrocytes from 7 donors, including 4 patients with Parkinson's disease who carry the LRRK2 G2019S mutation, and 3 healthy control individuals
RNA sequencing reveals MMP2 and TGFB1 downregulation in LRRK2 G2019S Parkinson's iPSC-derived astrocytes.
Sex, Specimen part, Cell line, Subject
View SamplesWe stratified colorectal tumor samples using a new unsupervised, iterative method based on non-negative matrix factorization (NMF). The resulting five subtypes exhibited activation of specific signaling pathways, and significant differences in microsatellite status and tumor location. We could also align three CRC cell lines panels to these subtypes.
Subtypes of primary colorectal tumors correlate with response to targeted treatment in colorectal cell lines.
Sex, Race
View SamplesGene expression analysis in control and diabetic rats. Diabetes-induced erectile dysfunction in rat model of DM. 10 weeks of streptozotocin induced diabetes. F344 Rats.
Microarray analysis reveals novel gene expression changes associated with erectile dysfunction in diabetic rats.
No sample metadata fields
View SamplesAddition of 3 new arrays made from carbon limited chemostat of CENPK113-7D and 3 new arrays made from aerobic carbon limited chemostat of CENPK113-7D Complmentary data to the data of the serie GSE1723.
Exploiting combinatorial cultivation conditions to infer transcriptional regulation.
No sample metadata fields
View SamplesWe report RNA-sequencing data of 283 blood platelet samples, including 228 tumor-educated platelet (TEP) samples collected from patients with six different malignant tumors (non-small cell lung cancer, colorectal cancer, pancreatic cancer, glioblastoma, breast cancer and hepatobiliary carcinomas). In addition, we report RNA-sequencing data of blood platelets isolated from 55 healthy individuals. This dataset highlights the ability of TEP RNA-based ''liquid biopsies'' in patients with several types with cancer, including the ability for pan-cancer, multiclass cancer and companion diagnostics. Overall design: Blood platelets were isolated from whole blood in purple-cap BD Vacutainers containing EDTA anti-coagulant by standard centrifugation. Total RNA was extracted from the platelet pellet, subjected to cDNA synthesis and SMARTer amplification, fragmented by Covaris shearing, and prepared for sequencing using the Truseq Nano DNA Sample Preparation Kit. Subsequently, pooled sample libraries were sequenced on the Illumina Hiseq 2500 platform. All steps were quality-controlled using Bioanalyzer 2100 with RNA 6000 Picochip, DNA 7500 and DNA High Sensitivity chips measurements. For further downstream analyses, reads were quality-controlled using Trimmomatic, mapped to the human reference genome using STAR, and intron-spanning reads were summarized using HTseq. The processed data includes 285 samples (columns) and 57736 ensemble gene ids (rows). The supplementary data file (TEP_data_matrix.txt) contains the intron-spanning read counts, after data summarization by HTseq.
RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics.
No sample metadata fields
View SamplesMicroarray studies revealed that as a first hit, SV40 T/t-antigen causes deregulation of 462 genes in mammary gland cells (ME-cells) of WAP-SVT/t transgenic animals. The majority of deregulated genes are cell-proliferation specific and Rb-E2F dependent, causing ME-cell proliferation and gland hyperplasia but not breast cancer formation. In the breast tumor cells, a further 207 genes are differentially expressed, most of them belonging to the cell communication category. In tissue culture, breast tumor cells frequently switch off WAP-SVT/t transgene expression and regain the morphology and growth characteristics of normal-ME-cells, although the tumor-revertant cells are aneuploid and only 114 genes regain the expression level of normal-ME-cells. The profile of retransformants shows that only 38 deregulated genes appear to be tumor-relevant and that none of them is considered to be a typical breast cancer gene.
Gene expression profiling: cell cycle deregulation and aneuploidy do not cause breast cancer formation in WAP-SVT/t transgenic animals.
No sample metadata fields
View SamplesPurpose: To identify the molecular phenotype of endothelial cells (EC) isolated from the unique vasculature of the corpus cavernosum.
Transcriptional profiling of human cavernosal endothelial cells reveals distinctive cell adhesion phenotype and role for claudin 11 in vascular barrier function.
Sex, Specimen part
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