Regulation of genes in shoots and roots and Arabidopsis in response to Zn-deficiency in wild-type and hma2 hma4 mutants plants
Systemic Upregulation of MTP2- and HMA2-Mediated Zn Partitioning to the Shoot Supplements Local Zn Deficiency Responses.
Age, Specimen part
View SamplesWe have determined that tenascin C (TNC) regulates the growth of human brain tumor initiating cells (BTICs). We have identified novel mechanisms by which TNC regulates BTIC growth. Analysis of the array data identified a number of genes that were altered with TNC treatment that could potentially regulate BTIC growth. The study provides the mechanistic basis for the regulation of BTIC growth with TNC.
Activation of NOTCH Signaling by Tenascin-C Promotes Growth of Human Brain Tumor-Initiating Cells.
Specimen part, Cell line, Treatment
View SamplesThis study utilise the examination of normal gastro-intestinal tissues to determine a tissue specific signal for use in deriving the intestinal signature of intestinal metaplasias of the oesophagus. Normal oesophageal, colonic and duodenal tissue biopsies were taken after informed consent and RNA was extracted following histological examination of adjacent tissues for normal aperaing mucosa.
The characterization of an intestine-like genomic signature maintained during Barrett's-associated adenocarcinogenesis reveals an NR5A2-mediated promotion of cancer cell survival.
Specimen part
View SamplesCeliac disease (CeD) is an intestinal immune-mediated disorder caused by gluten ingestion in genetically predisposed subjects. CeD is characterized by villous atrophy, altered intestinal permeability, crypt hyperplasia and innate and adaptive immune response. This study aimed to develop and validate the use of intestinal organoids from celiac patients to study CeD. A repository of organoids from duodenum of non-celiac and celiac patients was generated and characterized accordingly to standard procedures. RNA-seq analysis was employed to study the global gene expression program of CeD (n=3) and non-CeD (n=3) organoids sets. While the three celiac derived organoids shared similar transcriptional signatures the NC samples set appeared more heterogeneous. We found 486 genes differentially expressed between the two groups. Of them, 299 genes were downregulated (FC<2; FDR<0.05) and 187 were upregulated in CeD (FC >2; FDR<0.05). We observed CeD organoids had significantly altered expression of genes associated with barrier function, innate immunity, and stem cell function. Overall design: mRNA profiles of 3 non-celiac healthy controls and 3 celiac organoids derived from duodenal biopsies.
Human gut derived-organoids provide model to study gluten response and effects of microbiota-derived molecules in celiac disease.
Specimen part, Disease, Subject
View SamplesBACKGROUND
Emmprin and survivin predict response and survival following cisplatin-containing chemotherapy in patients with advanced bladder cancer.
No sample metadata fields
View SamplesRadiotherapy is widely used to treat human cancer. Patients locally recurring after radiotherapy, however, have increased risk of metastatic progression and poor prognosis. The clinical management of post-radiation recurrences remains an unresolved issue. Tumors growing in pre-irradiated tissues have an increased fraction of hypoxic cells and are more metastatic, a condition known as tumor bed effect. Here we demonstrate that tumor cells growing in a pre-irradiated bed, or selected in vitro though repeated cycles of severe hypoxia, retain an invasive and metastatic capacities when returned to normoxia. HIF activity, while it facilitates metastatic spreading of tumors growing in a pre-irradiated bed, is not essential. Through gene expression profiling and gain and loss of function experiments, we identified the matricellular protein CYR61 and aVb5 integrin, as proteins cooperating to mediate these effects. Inhibition of aVb5 integrin suppressed invasion and metastasis induced by CYR61 and attenuated metastasis of tumors growing within a pre-irradiated field. These results represent a conceptual advance to the understanding of the tumor bed effect and identify CYR61 and aVb5 integrin as proteins that co-operate to mediate metastasis. They also indicate aV integrin inhibition a potential therapeutic approach for preventing metastasis in patients at risk for post-radiation recurrences, which can be promptly tested in the clinic.
CYR61 and alphaVbeta5 integrin cooperate to promote invasion and metastasis of tumors growing in preirradiated stroma.
No sample metadata fields
View SamplesThe objective of this study was to make use of gene expression signatures and functional assays to delineate differences between various intestinal colon carcinoma cell lines and normal intestinal epithelium to assess their appropriateness as a tumor model or for drug absorption studies.
Defining new criteria for selection of cell-based intestinal models using publicly available databases.
Specimen part, Cell line
View SamplesAim: To examine transcriptional changes in DLD-1 cells exposed to softer matrices (2 kPa and 55 kPa) and identify the chromosomes that are enriched with maximmally deregulated genes Methods: DLD-1 cells (otherwise growing on stiff tissue culture plastic substrates) were exposed to softer matrices for 90 minutes and to collagen coated glass coverslips (served as control) served as control) Results: RNA sequencing revealed nearly equivalent transcriptional deregulation in cells on both the polyacrylamide matrices (783 genes up and 872 genes down on 2 kPa, 649 genes up and 783 genes down on 55 kPa) when compared to cells on glass. Additionally, GO classification revealed that unique sets of transcriptionally deregulated genes (log fold=2) belonged to pathways associated with transcription regulation, chromatin organization, cell cycle and DNA damage/repair Results: We identified chromosomes 1, 2, 3, 6, 7, 10, 12, 14, 17 and 19 to be maximally enriched with the deregulated genes on softer matrices (log fold=2), while chromosomes 13, 18 and 21 showed minimal enrichment of deregulated genes. We also examined the spatial organization of chromosome 1, 18 and 19 territories in cells on softer matrices (using 3D-FISH) and observed that these chromosomes were mislocalized away from their conserved nuclear locations Conclusions: Our study reports the transcriptomic changes in DLD-1 cells upon lowering of extracellular substrate stiffnes and its impact on the spatial positioning of chromosome territories Overall design: RNA Seq profiles for DLD-1 cells on soft polyacrylamide matrices of ~2 kPa and ~55 kPa (reference - glass) were generated across 2 independent biological replicates using Illumina HiSeq platform
Emerin modulates spatial organization of chromosome territories in cells on softer matrices.
Cell line, Subject
View SamplesExposures to dioxin, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause a wide array of toxicities in vertebrates and is mostly considered to be mediated through the inappropriate activation of the aryl hydrocarbon receptor (Ahr) signaling pathway. Although transcriptional regulation by Ahr is widely studied, the molecular mechanisms responsible for the adverse outcomes after Ahr activation are largely unknown. To identify the important events downstream of AHR activation that play an actual role in the toxic responses, we employed the zebrafish caudal fin regeneration models since Ahr activation blocks the regenerative process. Zebrafish regenerate their caudal fins by an orchestrated progression of cell migration, differentiation and proliferation controlled by a multitude of signaling pathways. This complex process was exploited as an in vivo platform to identify cross talk between Ahr and other signaling pathways. Global genomic analysis was performed in the larval regenerating fin tissue after exposure to TCDD in order to identify genes differentially regulated after Ahr activation. Comparative toxicogenomic analysis revealed that both adult and larval fins respond to TCDD during regeneration with mis-expression of Wnt signaling pathway members and Wnt target genes.
Crosstalk between AHR and Wnt signaling through R-Spondin1 impairs tissue regeneration in zebrafish.
No sample metadata fields
View SamplesEarly environmental experiences and life histories profoundly influence adult phenotypes via as yet poorly understood mechanisms. We previously showed that wild-type adult C. elegans that transiently passed through the stress-induced dauer larval stage (post-dauers) exhibit different gene expression patterns, genome-wide chromatin structure, and life history traits when compared to adults that bypassed the dauer stage (controls). Here we show that endogenous small inhibitory RNAs (endo-siRNAs) and siRNA pathways may mediate developmental history-dependent phenotypic diversity. Deep sequencing of small RNA libraries show changes in endo-siRNA levels in post-dauer as compared to control animals, and meta analyses indicate that specific endo-siRNA pathways are targets of developmental history-dependent reprogramming. We demonstrate that mutations in specific endo-siRNA pathways affect the expected gene expression and chromatin state changes in post-dauer animals, and also disrupt their increased brood size phenotype. We find that the chromatin state and endo-siRNA distribution in dauers is also distinct and suggest that this remodeling in dauers provides a template for the subsequent establishment of adult post-dauer profiles. Together, our results imply a critical mechanistic role for endo-siRNA pathways in mediating early experience-dependent phenotypic divergence in adults, and suggest that regulation of these pathways contribute to increased fitness via non-genetic mechanisms. Overall design: We deep-sequenced small RNA libraries from 2 biological replicates each of control and postdauer adults, and one biological each of larval L3 and dauer stages.
Developmental programming modulates olfactory behavior in C. elegans via endogenous RNAi pathways.
Cell line, Subject
View Samples