This SuperSeries is composed of the SubSeries listed below.
ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup.
Specimen part
View SamplesGene expression profiling of PanNETs patients samples were performed to understand genotype to phenotype correlations, novel molecular subtypes and cell of origin
ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup.
Specimen part
View SamplesThe most commonly mutated genes in pancreatic neuroendocrine tumors (PanNETs) are ATRX, DAXX, and MEN1. Little is known about the cells-of-origin for non-functional neuroendocrine tumors. Here, we genotyped 64 PanNETs for mutations in ATRX, DAXX, and MEN1 and found 37 tumors (58%) carry mutations in these three genes (A-D-M mutant PanNETs) and this correlates with a worse clinical outcome than tumors carrying the wild-type alleles of all three genes (A-D-M WT PanNETs). We performed RNA sequencing and DNA-methylation analysis on 33 randomly selected cases to reveal two distinct subgroups with one group consisting entirely of A-D-M mutant PanNETs. Two biomarkers differentiating A-D-M mutant from A-D-M WT PanNETs were high ARX gene expression and low PDX1 gene expression with PDX1 promoter hyper-methylation in the A-D-M mutant PanNETs. Moreover, A-D-M mutant PanNETs had a gene expression signature related to that of alpha cells (pval < 0.009) of pancreatic islets including increased expression of HNF1A and its transcriptional target genes. This gene expression profile suggests that A-D-M mutant PanNETs originate from or transdifferentiate into a distinct cell type similar to alpha cells. Overall design: Evaluation of Cell of origins for non-functional PanNETs and genotype to phenotype correlations in PanNETs
ATRX, DAXX or MEN1 mutant pancreatic neuroendocrine tumors are a distinct alpha-cell signature subgroup.
Specimen part, Subject
View SamplesBackground: The Epithelial Cell Adhesion Molecule (EpCAM) has been shown to be strongly expressed in human breast cancer and cancer stem cells and its overexpression has been supposed to support tumor progression and metastasis. However, effects of EpCAM overexpression on normal breast epithelial cells have never been studied before. Therefore, we analyzed effects of transient adenoviral overexpression of EpCAM on proliferation, migration and differentiation of primary human mammary epithelial cells (HMECs).
EpCAM overexpression prolongs proliferative capacity of primary human breast epithelial cells and supports hyperplastic growth.
Specimen part
View SamplesIntroduction: The Epithelial Cell Adhesion Molecule (EpCAM) has been shown to be strongly expressed in human breast cancer and cancer stem cells and its overexpression has been supposed to support tumor progression and metastasis. However, effects of EpCAM overexpression on normal breast epithelial cells have never been studied before. Therefore, we analyzed effects of transient adenoviral overexpression of EpCAM on proliferation, migration and differentiation of primary human mammary epithelial cells (HMECs).
EpCAM overexpression prolongs proliferative capacity of primary human breast epithelial cells and supports hyperplastic growth.
Specimen part, Subject
View SamplesBrassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helixloophelix transcription factor CESTA (CES) can contribute to the constitutive expression of the C-REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF-independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the posttranslational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation.
Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants.
Age, Specimen part, Treatment
View SamplesThe maturation of dendritic cells (DCs) after exposure to microbial products or inflammatory mediators plays a critical role in initiating the immune response. We found that maturation can also occur under steady state conditions, triggered by alterations in E-cadherin-mediated DC-DC adhesion. Selective disruption of these interactions induced the typical features of DC maturation including the upregulation of costimulatory molecules, MHC class II, and chemokine receptors. These events were triggered at least in part by activation of the b-catenin pathway. However, unlike maturation induced by microbial products, E-cadherin-stimulated DCs failed to release immunostimulatory cytokines, exhibiting an entirely different transcriptional profile. As a result, E-cadherin-stimulated DCs elicited an entirely different T cell response in vivo, generating T cells with a regulatory as opposed to an effector phenotype. These DCs induced tolerance in vivo and may thus contribute to the elusive steady state tolerogenic DCs.
Disruption of E-cadherin-mediated adhesion induces a functionally distinct pathway of dendritic cell maturation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells.
Specimen part
View SamplesTranscription factor-mediated reprogramming yields induced pluripotent stem cells (iPSC) by erasing tissue specific methylation and re-setting DNA methylation status to an embryonic stage. We compared bona fide human iPSC derived from umbilical cord blood (CB) and neonatal keratinocytes (K). Through both incomplete erasure of tissue specific methylation and de novo tissue specific methylation, CB-iPSC and K-iPSC are distinct in genome-wide DNA methylation profiles. Functionally, CB-iPSC displayed better blood formation in vitro, whereas K-iPSC differentiated better to a keratinocyte fate, implying that the tissue of origin needs to be considered in future therapeutic applications of human iPSCs.
Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells.
Specimen part
View SamplesThrough a loss-of-function approach, we identified that inhibition of the histone methyltransferase, Dot1L, accelerated somatic cell reprogramming, significantly increased the yield of induced pluripotent stem (iPS) cell colonies, and substituted for Klf4 and c-Myc in the reprogramming cocktail. To understand the mechanism by which Dot1L inhibition results in these phenotypes, we carried out gene expression profiling using Affymetrix microarrays.
Chromatin-modifying enzymes as modulators of reprogramming.
Specimen part, Treatment
View Samples