Drosophila PTB (Polypyrimidine Tract-binding protein dmPTB) regulates dorso-ventral patterning genes in embryos Overall design: Comparison of wild type (yw genotype) and PTB mutant (heph03429) drosophila embryos
Drosophila polypyrimidine tract-binding protein (DmPTB) regulates dorso-ventral patterning genes in embryos.
Sex, Specimen part, Subject
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Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Specimen part, Cell line, Treatment, Subject
View SamplesWe conducted an in vivo genome-wide CRISPR activation screen to identify genes that accelerate distal metastasis by breast cancer patient-derived circulating tumor cells (CTCs) following direct intravascular inoculation in mice. Regulators of translation and ribosomal proteins were prominent among these, and expression of RPL15, a component of the large ribosome subunit, was sufficient to increase metastatic growth in multiple organs. RPL15 overexpression selectively increases translation of other ribosomal proteins and cell cycle regulators. Unsupervised analysis of single-cell RNA sequencing of freshly-isolated CTCs from breast cancer patients identifies a subset with strong ribosomal and protein translation signatures, correlated with increased proliferative markers, epithelial markers and poor clinical outcome. Thus, ribosome protein expression identifies an aggressive subset of CTCs, whose therapeutic targeting may suppress metastatic progression.
Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Specimen part, Cell line, Treatment
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
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Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Specimen part, Cell line
View SamplesIntra-tumor heterogeneity is a hallmark of glioblastoma multiforme, and thought to negatively affect treatment efficacy. Here we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability between clones, including a wide range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-to-mesenchymal shift in the transcriptome.
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Specimen part, Cell line
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.
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View SamplesThe two immune cell populations Myeloid-derived suppressor cells (MDSCs), monocytes (MONO) and neutrophils (PMNs) are difficult to differentiate because of shared surface marker expression. Here we utilize the integrin receptor CD11b combined with conventional Ly6G and Ly6C expression to more accurately separate cellular populations via FACS. Then we apply high-throughput RNA Sequencing to Ly6G+Ly6C+CD11bhigh MDSC, Ly6G+Ly6C+CD11blow PMN and Ly6G-Ly6C+ monocyte populations. A total of 6,466 genes were significantly differentially expressed in MDSCs vs. monocytes, whereas only 297 genes were significantly different between MDSCs and PMNs. A number of genes implicated in cell cycle regulation were identified, and in vivo EdU labeling revealed that over 75% of MDSCs proliferated locally at the site of S. aureus biofilm infection. Overall design: RNA-Seq of myeloid-derived suppressor cells (MDSCs), neutrophils (PMNs), and monocytes during S. aureus biofilm infection in mice
Heterogeneity of Ly6G<sup>+</sup> Ly6C<sup>+</sup> Myeloid-Derived Suppressor Cell Infiltrates during Staphylococcus aureus Biofilm Infection.
Specimen part, Cell line, Subject
View SamplesThe experiment aims to identify mRNAs illustrating the unique nature of the gd T-cell subtype
Human Vδ2 T cells are a major source of interleukin-9.
Specimen part
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.
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