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GSE17354
Homo sapiens
13 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene transfer into HSCs by gammaretroviral vectors (RV) is an effective treatment for inherited blood disorders, although potentially limited by the risk of insertional mutagenesis. We evaluated the genomic impact of RV integration in T-lymphocytes from adenosine deaminase (ADA)-Severe combined immunodeficiency (SCID) patients 10 to 30 months after infusion of autologous, genetically-corrected CD34+ cells. Expression profiling on ex vivo T-cell bulk population revealed no difference with respect to healthy controls. To assess the effect of vector integration on gene expression at the single cell level, primary T-cell clones were isolated from two patients. T-cell clones harboured either one or two vector copies per cell and displayed partial to full correction of ADA expression, purine metabolism and TCR-driven functions. Analysis of retroviral integration sites (RIS) indicated a high diversity in T-cell origin, consistent with the polyclonal TCR-Vbeta repertoire. Quantitative transcript analysis of 120 genes within a 200kb-window around RIS showed modest (2.8- to 5.2-fold) disregulation of 5.8% genes in 18.6% of the T-cell clones compared to controls. Nonetheless, affected clones maintained a stable phenotype and normal functions in vitro. These results confirm that RV-mediated gene transfer for ADA-SCID is safe, and provide crucial information for the development of future gene therapy protocols.
Publication Title
Integration of retroviral vectors induces minor changes in the transcriptional activity of T cells from ADA-SCID patients treated with gene therapy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We devised a novel insertional mutagenesis approach based on lentiviral vectors to induce hepatocellular carcinoma in three mouse models and identified four novel cancer initiating genes. Two genes are the well characterized Braf and Sos1, while the other two are Fign, encoding an AAA ATPase whose functions are poorly understood, and the paternally expressed gene Rtl1 within the complex Dlk1-Dio3 imprinted region recently involved in stemness. Interestingly, Fign and Braf regulate the expression of the maternal genes of the Dlk1-Dio3 imprinted region, suggesting that both maternally and paternally expressed genes of this region play a role in hepatocarcinogenesis. Moreover, all the genes identified are upregulated and/or amplified/deleted in human hepatocellular carcinoma and play a relevant role in human hepatocarcinogenesis, as their expression levels and/or transcriptional signatures induced by their deregulation predict a different clinical outcome in hepatocellular carcinoma patients.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 29 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We devised a novel insertional mutagenesis approach based on lentiviral vectors to induce hepatocellular carcinoma in three mouse models and identified four novel cancer initiating genes. Two genes are the well characterized Braf and Sos1, while the other two are Fign, encoding an AAA ATPase whose functions are poorly understood, and the complex Dlk1-Dio3 imprinted region which has been recently implicated in cancer and stemness. Activation of Fign or Braf and upregulation of the Dlk1-Dio3 imprinted region are functionally interconnected and may altogether control cell transformation, stemness and energy metabolism. Moreover, all the genes identified play a relevant role in human hepatocarcinogenesis as their expression levels and/or transcriptional signatures induced by their deregulation predict a different clinical outcome in hepatocellular carcinoma patients. These series consists of mRNA expression microarray data (The GeneChip Mouse Gene 1.0 ST Array, Affymetrix) from 8 non-tumoral liver and 21 hepatocellular carcinoma induced by insertional mutagenesis.
Publication Title
Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This experiment was carried out in the context of a pharmacogenetic study of long-term (4-year follow-up) response to Interferon-beta treatment in two cohorts of Italian Multiple Sclerosis patients, to identify genetic variants (SNPs) that may influence response to IFN-beta. We integrated results from meta-analysis of the two cohorts with gene expression profiling of IFN stimulated PBMCs from 20 healthy controls and eQTL analyses, to look at possible enrichment of IFN-beta induced genes with genes mapped by top-ranking meta-analyzed SNPs.
Publication Title
Pharmacogenetic study of long-term response to interferon-β treatment in multiple sclerosis.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We exploited microarrays to detail the global program of gene expression underlying normal stem cells and cancer stem cells in the cerebellum and in medulloblastomas (MBs).
Publication Title
Gene signatures associated with mouse postnatal hindbrain neural stem cells and medulloblastoma cancer stem cells identify novel molecular mediators and predict human medulloblastoma molecular classification.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We have generated mouse models of real CMT1B mutations in the gene encoding for myelin protein zero (P0). One of these mutants, P0S63del is retained in the ER where it elicits an unfolded protein response (UPR). Genetic ablation of the UPR factor CHOP restores the motor capacity in S63del mice. We used microarray to decipher the molecular mechanism undelying the P0S63del neuropathy and the rescue in S63del/Chop null nerves.
Publication Title
Resetting translational homeostasis restores myelination in Charcot-Marie-Tooth disease type 1B mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD1d expression by thymocytes is required to select iNKT cells. When CD1d is expressed only on thymocytes (pLck-CD1d tg mice), iNKT cells are hyperresponsive to antigen stimulation suggesting that, in physiological conditions, these cells undergo functional education mediated by additional CD1d-expressing cells. Here, we investigated the mechanisms of this functional education. We find that peripheral iNKT cells from pLck-CD1d tg mice express significantly less SHP-1, a tyrosine phosphatase negatively regulating TCR signaling, than WT cells. iNKT cells from heterozygous SHP-1-mutated motheaten mice, displaying similar SHP-1 reduction as pLck-CD1d tg iNKT cells, are antigen-hyperresponsive. Restoring normal CD1d expression in pLck-CD1d tg mice normalizes SHP-1 expression and responsiveness of iNKT cells. In WT mice, iNKT cells upregulate SHP-1 and decrease responsiveness upon emigration from thymus to periphery. This depends on contacts with CD1d-expressing DCs. iNKT cell functional education is therefore controlled by DCs via tuning SHP-1 expression level in the periphery.
Publication Title
Functional education of invariant NKT cells by dendritic cell tuning of SHP-1.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Gene expression profiling following different learning paradigms may help in defining the moleular pathways of memory formation. In this study we analyzed the gene expression pattern of murine hippocampus at different time points (0.5 h, 2h, 6h) after trace fear conditioning. We compared trained mice with naive mice that remained in their homecages.
Publication Title
Temporal gene expression profile of the hippocampus following trace fear conditioning.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Goal of the analysis was to identify the mechansisms accounting fo the synergy of T cells redirected to the tumor associated large T antigen and T cells redirected to the Uty minor histocompatibility antigen
Publication Title
T Cells Redirected to a Minor Histocompatibility Antigen Instruct Intratumoral TNFα Expression and Empower Adoptive Cell Therapy for Solid Tumors.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Tmprss6 is the master inhibitor of hepcidin and its inactivation causes iron refractory iron deficiency anemia both in human and in mice. Mice with iron deficiency anemia (IDA)-low hepcidin show a pro-inflammatory response that is blunted in iron deficienct-high hepcidin Tmprss6 null mice. We investigated the transcriptional response associated with chronic hepcidin overexpression by comparing whole genome transcription profiling of the liver of Tmprss6 KO mice and IDA animals, irrespective of iron deficiency.
Publication Title
A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- mice.
Sample Metadata Fields
Age, Specimen part
View Samples