Since fibroblasts are a key component of the stroma with an established role in cancer, we investigated the contribution of fibroblasts to the signature observed in the stromal compartment. 13 clonally derived primary stromal fibroblasts were generated from metaplasia, dysplasia and EAC specimens. Expression of a panel of known fibroblast markers and concomitant absence of epithelial markers confirmed their fibroblastic origin. Gene expression profiling of these esophageal fibroblasts demonstrated that three ontologies related to an invasive phenotype (chemotaxis, cell adhesion, regulation of angiogenesis) differentiated cancer associated from BE fibroblasts. Furthermore, the ontologies and KEGG pathways relating to inflammation were all statistically upregulated in the fibroblast signature.
Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers.
Sex, Age, Specimen part, Disease
View SamplesWe recently reported that single-cell derived isogenic subclones of SKMEL5 cells have differential initial sensitivity to BRAF-inhibitors. In order to probe differences among these subclones, we selected three subclones with unique drug responses: progressing (SK-MEL-5 SC10), stationary (SK-MEL-5 SC07), and regressing (SK-MEL-5 SC01) and performed RNASeq. This study examines differentially expressed genes (DEGs) among the subclones to identify the molecular basis for initial differences in drug sensitivity. Overall design: Transcriptomics analysis between single-cell derived isogenic subclones of BRAF-mutated melanoma cell line, SK-MEL-5
A Nonquiescent "Idling" Population State in Drug-Treated, BRAF-Mutated Melanoma.
Specimen part, Cell line, Subject
View SamplesPromoter hypermethylation and transcriptional silencing is a common epigenetic mechanism of tumour suppressor inactivation in cancer, including malignant brain tumours.
Epigenetic genome-wide analysis identifies BEX1 as a candidate tumour suppressor gene in paediatric intracranial ependymoma.
Specimen part, Treatment
View SamplesUnderstanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor gammat (RORgammat) transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We identified a novel cell subset of CD56dimNKp46low cells that includes RORgammat+ILCs with a lineage-CD94-CD117brightCD127bright phenotype.We also included data regarding the genome-wide transcriptional profiles of human healthy colonic NK cells and RORgammat+ILCs.The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases.
Mapping of NKp46(+) Cells in Healthy Human Lymphoid and Non-Lymphoid Tissues.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells.
Cell line, Treatment
View SamplesEpithelial to mesenchymal transition (EMT) is activated during cancer invasion and metastasis, enriches for cancer stem cells (CSCs), and contributes to therapeutic resistance and disease recurrence. The epithelial cell line MCF7, can be induced to undergo EMT with the induction of PKC by PMA. 5-10% of the resulting cells have a CSC phenotype. This study looks at the transcriptome of these cells and how it differs from cells with a non-CSC phenotype.
Chromatinized protein kinase C-θ directly regulates inducible genes in epithelial to mesenchymal transition and breast cancer stem cells.
Cell line, Treatment
View SamplesEffect of the ablation of connexin 30 in the stria vascularis
Connexin30 deficiency causes instrastrial fluid-blood barrier disruption within the cochlear stria vascularis.
Age, Specimen part, Disease, Time
View SamplesTo assess the effect of activation of the unfolded protein response (UPR) in colon cancer cell lines, we treated cells with the AB5 subtilase cytotoxin (SubAB). This proteolytically cleaves the 78-kDa glucose-regulated protein (GRP78; also known as HSPA5 or BiP) inside the endoplasmic reticulum. We find that the WNT signaling pathway is highly affected upon treatment with SubAB.
ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response.
Specimen part, Cell line, Treatment
View SamplesComparison of gene expression profile of Ewing sarcoma cells which have an exchange of the endogenous EWS/FLI1 to either wild-type or a turnover-deficient mutant EWS/FLI1. Most target genes are saturated as only a few target genes are soly driven by increasing protein amount.
Proteasomal Degradation of the EWS-FLI1 Fusion Protein Is Regulated by a Single Lysine Residue.
No sample metadata fields
View SamplesNatural killer (NK) cells are NKp46+CD3- lymphocytes that can perform granule-dependent cytotoxicity and produce interferon-gamma, when isolated from blood, lymphoid organs, lung, liver and uterus. Here we identify in dermis, gut lamina propria and cryptopatches, very distinct populations of NKp46+CD3- cells with reduced ability to degranulate and to produce interferon-gamma. In gut, the transcription factor RORgamma-t and CD127 (IL-7R alpha) defined a novel subset of NKp46+CD3- that is reminiscent of lymphoid tissue inducer (LTi)-like cells. Gut ROR gamma t+NKp46+ cells produced IL-22 in contrast to ROR-gamma t-independent lamina propria and dermis NK cells. These data show that LTi-like cells and NK cells share unanticipated similarities and reveal the heterogeneity of NKp46+CD3- cells in innate immunity, lymphoid organization and local tissue repair.
Influence of the transcription factor RORgammat on the development of NKp46+ cell populations in gut and skin.
Sex, Age
View Samples