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GSE30219
Homo sapiens
299 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An unexplored consequence of epigenetic alterations associated with cancer is the ectopic expression of tissue-restricted genes. Here, a new strategy was developed to decipher genome-wide expression data in search for these off-context gene activations, which consisted first, in identifying a large number of tissue-specific genes normally epigenetically silenced in most somatic cells and second, in using them as cancer biomarkers on an on/off basis. Applying this concept to analyze whole-genome transcriptome data in lung cancer, we discovered a specific group of 26 genes whose expression was a strong and independent predictor of poor prognosis in our cohort of 293 lung tumours, as well as in two independent external populations. In addition, these 26 classifying genes enabled us to isolate a homogenous group of metastatic-prone highly aggressive tumours, whose characteristic gene expression profile revealed a high proliferative potential combined to a significant decrease in immune and signaling functions. This work illustrates a new approach for a personalized management of cancer, with applications to any cancer type.
Publication Title
Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Precociously disseminated cancer cells may seed quiescent sites of future metastasis if they can protect themselves from immune surveillance. However, there is little knowledge about how such sites might be achieved. Here we present evidence that prostate cancer stem-like cells (CSC) can be found in histopathologically negative prostate draining lymph nodes (PDLN) in mice harboring oncogene-driven prostate intraepithelial neoplasia (mPIN). PDLN-derived CSC were phenotypically and functionally identical to CSC obtained from mPIN lesions, but distinct from CSCs obtained from frank prostate tumors. CSC derived from either PDLN or mPIN used the extracellular matrix protein Tenascin-C (TNC) to inhibit T cell receptor-dependent T cell activation, proliferation and cytokine production. Mechanistically, TNC interacted with 51 integrin on the cell surface of T cells, inhibiting reorganization of the actin-based cytoskeleton therein required for proper T cell activation. CSC from both PDLN and mPIN lesions also expressed CXCR4 and migrated in response to its ligand CXCL12, which was overexpressed in PDLN upon mPIN development. CXCR4 was critical for the development of PDLN-derived CSC, as in vivo administration of CXCR4 inhibitors prevented establishment in PDLN of an immunosuppressive microenvironment. Taken together, our work establishes a pivotal role for TNC in tuning the local immune response to establish equilibrium between disseminated nodal CSC and the immune system.
Publication Title
Tenascin-C Protects Cancer Stem-like Cells from Immune Surveillance by Arresting T-cell Activation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
Illumina HiSeq 2000
Description
We performed RNA sequencing to assess changes in gene expression in lung cancer cell lines with MET genetic alterations with or without co-occurrence of JAK2 inactivating mutations. Different treatments have been administrated to activate or inhibit selected pathways in order to define MET signature and IFNg (or JAK/STAT) signature. Overall design: Differential expression analysis of RNA sequencing of 4 different lung cancer cell lines with MET genetic alterations treated with different treatements to activate or inhibit selected pathways
Publication Title
<i>MET</i>-Oncogenic and <i>JAK2</i>-Inactivating Alterations Are Independent Factors That Affect Regulation of PD-L1 Expression in Lung Cancer.
Sample Metadata Fields
Disease, Disease stage, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have identified SOX2 as a new oncogene and a likely driver of recurrent 3q26.3 amplifications in lung Squamous Cell Carcinoma. SOX2 is a crucial transcription factor implicated in Embryonic and Neural Stem Cells, that we found widely activatd in human lung SCC. This part of the study aimed at analyzing the transcriptomic consequences of SOX2 overexpression in a simple in vitro model (human lung squamous immortalized cells).
Publication Title
SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
In Multiple Sclerosis, the pathological interaction of autoreactive helper T (TH) cells with mononuclear phagocytes in the central nervous system (CNS) drives initiation and maintenance of chronic neuroinflammation. Herein, we found that intrathecal transplantation of neural stem cells (NPCs) in mice with experimental autoimmune encephalomyelitis (EAE) impairs the accumulation of inflammatory monocyte-derived dendritic cells (moDCs) in the CNS leading to improved clinical outcome. NPCs treatment reduced in the CNS IL-23, IL-1 and TNF-a, cytokines required for terminal differentiation of TH cells and accordingly GM-CSF-producing pathogenic TH cells. In vivo and in vitro transcriptome analyses disclosed that NPC secreted factors induce an inhibition of DC differentiation and maturation, favoring a fate switch towards an anti-inflammatory phenotype. We identified TGF-ß2 as the crucial mediator of NPC immunomodulation: TGFß2 knockout NPCs transplanted in EAE are ineffective in impairing moDC accumulation within the CNS and fail to drive clinical improvement. This study provides evidence that intrathecally injected NPCs interfere with CNS-compartmentalized inflammation of the effector phase of EAE, reprogramming, through the secretion of TGF-ß2, inflammatory monocyte-derived DCs towards anti-inflammatory myeloid cells. Overall design: mRNA profiles of monocyte derived-dendritic cells (moDCs) isolated by FACS sorting at 7 days post-treatment from the CNS (hindbrain and spinal cord) of quadruplicate pool of 4–7 MOG35-55-immunized C57Bl/6 mice either intrathecally injected with PBS or 1 million neural precursor cells (NPCs) at the peak of the disease (2-4 days after clinical onset).
Publication Title
Neural precursor cell-secreted TGF-β2 redirects inflammatory monocyte-derived cells in CNS autoimmunity.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Background: Although TNF inhibitors are used to treat chronic inflammatory diseases, there is little information about how long-term inhibition of TNF affects the homeostatic functions that TNF maintains in the intact CNS. TNF is known to modulate neurogenesis by decreasing cell proliferation, increasing apoptosis of precursor cells, and impairing neuronal differentiation. TNF can also influence the formation of the hippocampus, with long-lasting effects on cognition. Materials and methods: To clarify whether developmental TNF deficiency causes alterations in the naïve CNS, we estimated the number of proliferating cells, microglia, and neurons in the brains of E13.5, P7, and adult TNF +/+ and TNF-/- mice and measured changes in gene and protein expression and monoamine levels in adult TNF+/+ and TNF-/- mice. To evaluate long-term effects of TNF inhibitors, we treated healthy adult C57BL/6 mice with either saline, selective soluble TNF inhibitor XPro1595, or nonselective TNF inhibitor etanercept. We estimated changes in cell number and protein expression after two months of treatment. We assessed the effects of TNF deficiency on cognition by testing adult TNF+/+ and TNF-/- mice and anti-TNF treated mice with behavioral tasks.
Publication Title
TNF deficiency causes alterations in the spatial organization of neurogenic zones and alters the number of microglia and neurons in the cerebral cortex.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This experiment was carried out in the context of a study aimed to identify the function of the transcription facotrs HIF-1a in the pathogenesis of chronic lymphocytic leukemia (CLL).
Publication Title
HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment.
Sample Metadata Fields
Sex, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We investigated the impact of on miR-H1 and miR-K12-3-3p- on host transcriptome focusing on gingival epithelial cells that are target sites for various HHV.
Publication Title
Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD4+ T cell help is critical for optimal CD8+ T cell expansion after priming in many experimental systems. However, a role for CD4+ T cells in regulating the initial steps of CD8+ T cell effector differentiation is not well established. Here we demonstrate that absence of CD4+ T cells at the time of replication-incompetent adenovirus vector immunization of C57BL/6 mice led to immediate CD8+ T cell dysfunction characteristic of exhaustion at the first detectable timepoints as well as impaired expansion of antigen-specific CD8+ T cells. The absence of CD4+ T cell help resulted in antigen-specific CD8+ T cells that had reduced ex vivo cytotoxicity and decreased capacity to produce IFN- and TNF-. CD8+ T cells primed in the absence of CD4+ T cells expressed elevated levels of the inhibitory receptors PD-1, LAG-3, and Tim-3, and these cells exhibited transcriptomic exhaustion profiles by gene set enrichment analysis. This dysfunctional state was imprinted within 3 days of immunization and could not be reversed by provision of CD4+ T cell help after priming. Partial rescue of unhelped CD8+ T cell expansion and effector differentiation could be achieved by PD-1 pathway blockade or recombinant IL-2 administration.
Publication Title
Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells.
Sample Metadata Fields
Specimen part, Time
View Samples