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Homo sapiens
37 Downloadable Samples
Illumina HiSeq 4000
Description
Evidence from mouse chronic viral infection models suggests that CD8+ T cell subsets characterized by distinct expression levels of the receptor PD-1 diverge in their state of exhaustion and potential for reinvigoration by PD-1 blockade. However, it remains unknown whether T cells in human cancer adopt a similar spectrum of exhausted states based on PD-1 expression levels. We compared transcriptional, metabolic, and functional signatures of intratumoral CD8+ T lymphocyte populations with high (PD-1T), intermediate (PD-1N) and no PD-1 expression (PD-1-) from non-small cell lung cancer patients. We observed that, PD-1T T cells show a markedly different transcriptional and metabolic profile as compared to PD-1N and PD-1- lymphocytes, as well as an intrinsically high capacity for tumor recognition. Furthermore, while PD-1T lymphocytes are impaired in classical effector cytokine production, they produce CXCL13 that mediates immune cell recruitment to tertiary lymphoid structures. Strikingly, the presence of PD-1T cells was strongly predictive for both response and survival in a small cohort of non-small cell lung cancer patients treated with PD-1 blockade. The characterization of a distinct state of tumor-reactive, PD-1 bright lymphocytes in human cancer, which only partially resembles that seen in chronic infection, provides novel potential avenues for therapeutic intervention. Overall design: Intratumoral CD8+ T cells from 11 non-small cell lung cancer patients that were sub-sorted into PD1-high (PD-1T), PD1-intermediate (PD-1N) and PD1-negative (PD-1-) cells, were sequenced using Illumina HiSeq4000. In addition, peripheral blood effector memory T cells from 4 healthy donors were sequenced using Illumina HiSeq4000.
Publication Title
A transcriptionally and functionally distinct PD-1<sup>+</sup> CD8<sup>+</sup> T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Expression of the proendocrine gene neurogenin 3 (Ngn3) is required for the development of pancreatic islets. In order to better characterize the molecular events regulated by Ngn3 during development, we have determined the expression profile of differentiating murine embryonic stem cells (mESCs) uniformly induced to overexpress Ngn3. An ESC line was created that allows for the induction of Ngn3 by adding doxycycline (Dox) to the culture medium. Genome-wide microarray analysis was performed to identify genes regulated by Ngn3 in a variety of both undifferentiated and differentiated conditions. Characterization of pancreatic developmental markers during embryoid body (EB) formation revealed an optimum context for Ngn3 induction. Neuroendocrine genes including neurogenic differentiation 1 (NeuroD1) and single minded 1 (Sim1) were found to be significantly upregulated. Genes regulated by Ngn3 independent of the context were analyzed using systematic gene ontology tools and revealed Notch signaling as the most significantly regulated signaling pathway (p=0.009). This result is consistent with the hypothesis that Ngn3 expression makes the cell competent for Notch signaling to be activated and conversely, more sensitive to Notch signaling inhibition. Indeed, EBs induced to express Ngn3 were significantly more sensitive to gamma-secretase inhibitor-mediated Notch signaling inhibition (p<0.0001). Moreover, we find that Ngn3 induction in differentiating ESCs results in significant increases in insulin, glucagon, and somatostatin transcription.
Publication Title
Differentiation of embryonic stem cells conditionally expressing neurogenin 3.
Sample Metadata Fields
No sample metadata fields
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GSE4737- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Summary:
Publication Title
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
Sample Metadata Fields
No sample metadata fields
View Samples GSE2555- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A Array (hgu133a)
Description
HEK293 cells were transfected with control plasmid (pcDNAI/Neo;Invitrogen) or with the plasmid encoding HCaRG. Stable transfectants were synchronized and grown in the presence of 10% FBS for 48 h. Total RNAs were purified with the mini RNeasy kit (Qiagen).
Publication Title
HCaRG increases renal cell migration by a TGF-alpha autocrine loop mechanism.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
CD133 is expressed by a subpopulation of human fetal hair follicle placode cells during early hair development. Its expression, which is gradually lost as the placode matures, correlates with early morphogenesis.
Publication Title
CD133 expression correlates with membrane beta-catenin and E-cadherin loss from human hair follicle placodes during morphogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The SCL and LMO1 oncogenic transcription factors reprogram thymocytes into self-renewing pre-leukemic stem cells (pre-LSCs). Here we report that SCL directly interacts with LMO1 to activate the transcription of a self-renewal program coordinated by LYL1.
Publication Title
SCL, LMO1 and Notch1 reprogram thymocytes into self-renewing cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
This study examined the gene expression effects of treating androgen-deprived C4-2 prostate cancer cells with the ACLY inhibitor BMS-303141 and the AR antagonist enzalutamide. Overall design: Cells were treated with vehicle control, ACLY inhibitor alone, Enzalutamide alone, and ACLY-inhibitor and Enzalutamide combined together for 24 hours under androgen-depleted conditions (RPMI + 5% charcoal stripped serum). Biological triplicate samples were prepared.
Publication Title
Targeting ACLY sensitizes castration-resistant prostate cancer cells to AR antagonism by impinging on an ACLY-AMPK-AR feedback mechanism.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
RNA-sequencing from Aclyf/f and Acly-/- preadipocytes generated from Aclyf/f mice and induced to differentiate to adipocytes. Overall design: Examination of gene expression during adipocyte differentiation, with Acly intact or deleted
Publication Title
Adipocyte ACLY Facilitates Dietary Carbohydrate Handling to Maintain Metabolic Homeostasis in Females.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Drosophila Gene 1.1 ST Array (drogene11st)
Description
The Drosophila TRIM-NHL protein Brain tumor (Brat) plays important roles during early embryogenesis, in cell fate decisions, during neurogenesis and in mature neurons. Brat is an RNA-binding protein and functions as translational repressor. However, which RNAs Brat regulates and how RNA-binding specificity is achieved, is unknown. Using RNA-Immunoprecipitation we identify Brat-bound mRNAs in Drosophila embryos and define a consensus binding motif.
Publication Title
The Crystal Structure of the NHL Domain in Complex with RNA Reveals the Molecular Basis of Drosophila Brain-Tumor-Mediated Gene Regulation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
Background Alternative splicing (AS) is a central mechanism of genetic regulation which modifies the sequence of RNA transcripts in higher eukaryotes. AS has been shown to increase both the variability and diversity of the cellular proteome by changing the composition of resulting proteins through differential choice of exons to be included in mature mRNAs. Results In the present study, alterations to the global RNA splicing landscape of cellular genes upon viral infection were investigated through high-throughput RNA sequencing (RNA-seq) studies using mammalian reovirus as a model. Our study provides the first comprehensive portrait of global changes in the RNA splicing signatures that occur in eukaryotic cells following infection with a human virus. We identify modifications in the AS patterns of 240 cellular transcripts frequently involved in the regulation of gene expression and RNA metabolism. A significant number of the modified transcripts are also encoded by genes with important roles in viral infection/immunity. These modifications are expected to alter the functions of many cellular proteins. Finally, we used RT-PCR analysis in order to experimentally validate differential modifications in alternative splicing patterns that were observed through RNA-seq studies. Conclusion The present study demonstrated that viral infection can extensively modify the splicing patterns of numerous cellular transcripts. These findings provide additional insights into the complexity of virus-host interactions as these splice variants expand proteome diversity and function during viral infection. Finally, these data open new avenues of research for a better understanding of post-transcriptional events during virus infection and possible new targets toward the development of antiviral agents. Overall design: mRNAs were isolated from L929 mouse cell line, 14 hours after infection with T3D-S Reovirus or T3D-S Mutant reovirus at a MOI of 50. Control cells were uninfected. The resulting libraries were multiplexed and paired-end sequenced using Illumina HiSeq. Gene expression and alternative splicing were caracterized using Bowtie and RSEM.
Publication Title
Global Profiling of the Cellular Alternative RNA Splicing Landscape during Virus-Host Interactions.
Sample Metadata Fields
Specimen part, Cell line, Subject
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