We report the RNAseq data obtained from 50.000-100.000 CD31-/CD45- pneumocytes isolated by FACS from mice harboring a normal dose or one extra copy of the Sirt1 gene, and a tamoxifen-inducible oncogenic KI alelle of KRasG12V after 4 weeks of tamoxifen treatment. Pneumocytes with the activated form of the inducible KRasG12V oncogene sere selected making use of the reporter gene LacZ (located next to the oncogene in the same polycistronic mRNA), by loading CD31-/CD45- pneumocytes with the LacZ-activated fuorogenic molecule FDG prior to FACS sorting. Overall design: Four replicates of each genetic group (Sirt1-WT and Sirt1-Tg) pneumocytes were used for this study. Sirt1-WT were used as reference controls.
Sirt1 protects from K-Ras-driven lung carcinogenesis.
Subject
View SamplesWe report the RNAseq data obtained from 50.000-100.000 CD31-/CD45- pneumocytes isolated by FACS from mice harboring a normal dose or one extra copy of the Sirt1 gene, and a tamoxifen-inducible oncogenic KI alelle of KRasG12V after 4 weeks of tamoxifen treatment plus 2 weeks without tamoxifen. Pneumocytes with the activated form of the inducible KRasG12V oncogene sere selected making use of the fluorescent reporter gene Katushka (located at an independent locus), by detecting Katushka fluorescence. Overall design: Four replicates of each genetic group (Sirt1-WT and Sirt1-Tg) pneumocytes were used for this study. Sirt1-WT were used as reference controls.
Sirt1 protects from K-Ras-driven lung carcinogenesis.
Sex, Subject
View SamplesWe developed a computational framework that integrates chromosomal copy number and gene expression data for detecting aberrations that promote cancer progression. We demonstrate the utility of this framework using a melanoma dataset. Our analysis correctly identified known drivers of melanoma and predicted multiple novel tumor dependencies. Two dependencies, TBC1D16 and RAB27A, confirmed empirically, suggest that abnormal regulation of protein trafficking contributes to proliferation in melanoma. Together, these results demonstrate the ability of integrative Bayesian approaches to identify novel candidate drivers with biological, and possibly therapeutic, importance in cancer.
An integrated approach to uncover drivers of cancer.
Cell line
View SamplesBackground: Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs) are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM.
Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas.
Specimen part, Disease
View SamplesMechanical forces are essential for normal fetal lung development. However, the cellular and molecular mechanisms regulating this process remain largely unknown. In the present study, we used oligonucleotide microarray technology to investigate gene expression profile in cultured E19 rat fetal lung type II epithelial cells exposed to a level of mechanical strain similar to that observed in utero. Significance Analysis of Microarrays (SAM) identified 92 genes differentially expressed by strain. Interestingly, several members of the solute carrier family of amino acid transporters, genes involved in amino acid synthesis and development, and amiloride-sensitive epithelial sodium channel gene were induced by strain. These results were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Thus, this study identifies genes induced by strain that may be important for amino acid signaling pathways, protein synthesis and development in fetal type II cells. In addition, these data suggest that mechanical forces may contribute to facilitate lung fluid reabsorption in preparation for birth. Taken together, the present investigation provides further insights into how mechanical forces may modulate fetal lung development.
DNA microarray reveals novel genes induced by mechanical forces in fetal lung type II epithelial cells.
Sex, Specimen part
View SamplesVariant FhlA133 (Q11H, L14V, Y177F, K245R, M288K, and I342F) had eight- fold higher hydrogen production than FhlA wild-type under 30 min of anaerobic incubation in modified-complex 20 mM formate at 37C. The mechanism by which the FhlA133 mutations increase hydrogen production is by increasing the transcription of all of the genes activated by the native FhlA (FHL complex).
Protein engineering of the transcriptional activator FhlA To enhance hydrogen production in Escherichia coli.
No sample metadata fields
View SamplesLarge-scale genomic studies have identified multiple somatic aberrations in breast cancer, including copy number alterations, translocations, and point mutations. Still, identifying causal variants and emergent vulnerabilities that arise as a consequence of genetic alterations remain major challenges. We performed whole genome shRNA “dropout screens” on 77 breast cancer cell lines. Using a new hierarchical linear regression algorithm to score our screen results and integrate them with accompanying detailed genetic and proteomic information, we identify novel vulnerabilities in breast cancer, including new candidate “drivers,” and reveal general functional genomic properties of cancer cells. Comparisons of gene essentiality with drug sensitivity data suggest potential resistance mechanisms, novel effects of existing anti-cancer drugs, and new opportunities for combination therapy. Finally, we demonstrate the utility of this large dataset by identifying BRD4 as a potential target in luminal breast cancer, and PIK3CA mutations as a resistance determinant for BET-inhibitors. Additional formatted data can be found at http://neellab.github.io/bfg/. Code and tutorials for the siMEM algorithm can be found at http://neellab.github.io/simem/. Overall design: RNA-Seq expression profiling of 82 breast cancer cell lines without replicates or control samples
Functional Genomic Landscape of Human Breast Cancer Drivers, Vulnerabilities, and Resistance.
No sample metadata fields
View SamplesMechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. However, very little is known about the transcriptional regulators involved in HC fate determination and differentiation. In this paper, we show that expression of three HC lineage-specific transcription factors: Gfi1, Pou4f3 and Atoh1, can induce a direct commitment towards HC fate during in vitro embryonic stem cell (ESC) differentiation. Induced HCs (iHCs) express numerous HC-specific genes and exhibit polarized membrane protusions reminiscent of stereociliary bundles.
Generation of sensory hair cells by genetic programming with a combination of transcription factors.
Specimen part, Cell line
View SamplesThe data presented is intended to analyse the changes in the expression profiles of human MSCs (Mesenchymal Stromal/Stem Cells) associated to different tissue specific stimulus.
Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling.
Specimen part
View SamplesA number of studies find that metastasis suppressor proteins, including RhoGDI2, may function in part though controlling expression of genes regulating metastasis (reviewed in Smith and Theodorescu, Nature Reviews Cancer, 2009, PMID: 19242414). To uncover systematically gene expression patterns dependent on RhoGDI2 expression, we profiled gene expression in stably transfected control (GFP empty vector) UM-UC-3 bladder carcinoma cells (which have lost endogenous expression of RhoGDI2, as occurs commonly in the progression of bladder cancer PMID: 15173088), as well as stably transfected GFP-tagged RhoGDI2 expressing UM-UC-3 cells.
RhoGDI2 suppresses lung metastasis in mice by reducing tumor versican expression and macrophage infiltration.
Specimen part, Cell line
View Samples