This SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesAnalysis of the combined dataset of normal skin, actinic keratosis and cutaneous squamous cell carcinoma (cSCC) previously submitted in (GSE45216) at genomic/transciptomic level. We identified potential cSCC driver genes significantly mutated and upregulated in cSCC relative to normal skin.
No associated publication
Specimen part
View SamplesTranscriptomic profiling of peripheral immune cells can provide a wealth of information.
No associated publication
Sex, Age, Specimen part, Disease, Disease stage, Treatment
View SamplesImmunomodulatory drugs (IMiDs), such as lenalidomide provide a tool to enhance both direct anti-tumor and graft-versus-tumor effects after allogeneic haematopoietic stem-cell transplantation (AHCT). However, early clinical experience with IMiDs after AHCT using adult peripheral blood (APB) as a stem cell source has been limited by induction of graft-versus-host disease. Characterization of the mechanisms by which IMIDs can modulate alloresponses of T-cells from different cell sources could facilitate more effective use of these drugs in the setting of AHCT. In this study we have used in vitro modelling to identify changes in alloresponses of APB and umbilical cord blood (UCB) T-cells after exposure to the widely used IMiD lenalidomide. We demonstrate that lenalidomide increases net alloproliferation of APB T-cells by selectively enhancing allospecific proliferation of CD8+ T-cells. These CD8+ T-cells have enhanced effector memory differentiation, are enriched for polyfunctional effectors, and have a distinct gene expression profile with altered expression of key immunoregulatory genes. In contrast, although lenalidomide treatment of UCB T-cells results in a similar increase in alloreactive effector CD8+ T-cells, it also reduces allospecific proliferation of CD4+ T-cells and selectively expands frequencies of CD4+ regulatory T-cells, resulting in a net reduction in UCB T-cell alloproliferation. Our findings show that lenalidomide has a qualitatively different impact on alloresponses of T-cells from different cell sources, with a potentially tolerogenic effect on UCB T-cells. These findings have important implications for the future use of IMiDs in the setting of AHCT.
No associated publication
Specimen part, Treatment
View SamplesWe analysed gene expression in normal breast blood vessels and breast invasive ductal carinoma blood vessels.
No associated publication
Specimen part
View SamplesIdentifying the differentially expressed genes between ADI-PEG20 resistant and parental Ju77 cell line
Inhibition of the Polyamine Synthesis Pathway Is Synthetically Lethal with Loss of Argininosuccinate Synthase 1.
Cell line
View SamplesIntegration of multiple signals shapes cell adaptation to their microenvironment through synergistic and antagonistic interactions. The combinatorial complexity governing signal integration for multiple cellular output responses has not been resolved. For outputs measured in the conditions 0 (control), signals X, Y, X+Y, combinatorial analysis revealed 82 possible interaction profiles, which we biologically assimilated to 5 positive, and 5 negative interaction modes. To experimentally validate their use in living cells, we designed an original computational workflow, and applied it to transcriptomics data of innate immune cells integrating physiopathological signal combinations. Up to 9 of the 10 defined modes coexisted in context-dependent proportions. Each integration mode was enriched in specific molecular pathways, suggesting a coupling between genes involved in particular functions, and the corresponding mode of integration. We propose that multimodality and functional coupling are general principles underlying the systems level integration of physiopathological and pharmacological stimuli by mammalian cells.
Combinatorial code governing cellular responses to complex stimuli.
Time
View SamplesThe ontogeny of human Langerhans cells (LCs) remains poorly characterized, in particular the nature of LC precursors and the factors that may drive LC differentiation. Through a systematic transcriptomic analysis of TSLP-activated dendritic cells (DCs), we unexpectedly identified markers that have been associated with a skin-homing potential as well as with a LC phenotype. We performed transcriptomic analysis of TSLP-activated blood DCs, as compared to freshly purified, Medium-, and TNF-activated DCs. Among TSLP up-regulated genes, we identified molecules associated with skin homing, LC phenotype, and LC function, as determined by a literature-based survey. Conversely, genes not expressed in LCs were not found among TSLP-induced genes. Further experiments showed that TGF- synergized with TSLP leading to the differentiation of blood BDCA-1+ DCs into bona fide Birbeck granule-positive LCs.
Human blood BDCA-1 dendritic cells differentiate into Langerhans-like cells with thymic stromal lymphopoietin and TGF-β.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.
Sex, Age, Specimen part
View SamplesAlternative splicing is a key event to human transcriptome and proteome diversity and complexity. Recent evidence suggests that pancreatic cancer might possess particular patterns of splice variation that influence the function of individual genes contributing to tumour progression in this disease. The identification of new pancreatic cancer-associated splice variants would offer opportunities for novel diagnostics and potentially also represent novel therapeutic targets.
A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.
Sex, Age, Specimen part
View Samples