Oral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naïve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11b¬– cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11b– cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development. Overall design: Four dendritic cell subpopulations from mouse mesenteric lymphnodes were sorted and compared in their gene expression profile
Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance.
Specimen part, Cell line, Subject
View SamplesOral tolerance prevents pathological inflammatory responses towards innocuous foreign antigens via peripheral regulatory T cells (pTreg cells). However, whether a particular subset of antigen-presenting cells (APCs) is required during dietary antigen exposure to instruct naïve CD4+ T cells to differentiate into pTreg cells has not been defined. Using myeloid lineage-specific APC depletion in mice, we found that monocyte-derived APCs are dispensable, while classical dendritic cells (cDCs) are critical for pTreg cell induction and oral tolerance. CD11b¬– cDCs from the gut-draining lymph nodes efficiently induced pTreg cells, and conversely, loss of IRF8-dependent CD11b– cDCs impaired their polarization, although oral tolerance remained intact. These data reveal the hierarchy of cDC subsets in pTreg cell induction and their redundancy during oral tolerance development. Overall design: Sorted naïve CD45.1 OT-II CD4 T cells were co-cultured with four dendritic cell subpopulations sorted from mouse mesenteric lymphnodes. 24h later OT-II cells were sorted again and compared in their gene expression profile.
Classical dendritic cells are required for dietary antigen-mediated induction of peripheral T(reg) cells and tolerance.
Specimen part, Cell line, Subject
View SamplesIn the present study, we aimed to define the role of VDR in the overall lipid metabolism by transcriptomic and metabolomic analyses of human hepatocytes upon VDR activation by vitamin D (VitD)
The Vitamin D Receptor Regulates Glycerolipid and Phospholipid Metabolism in Human Hepatocytes.
Specimen part, Cell line, Treatment
View SamplesCOHCAP (City of Hope CpG Island Analysis Pipeline) is an algorithm to analyze single-nucleotide resolution DNA methylation data. It provides QC metrics, differential methylation for CpG Sites, differential methylation for CpG Islands, integration with gene expression data, and visualization of methylation values. COHCAP is currently the only DNA methylation package that can handle integration with gene expression data, and the results of this study show that COHCAP can identify regions of differential methylation with ~50% concordance with gene expression. COHCAP is scalable for analysis of both cell line data and heterogeneous patient data, and it can identify known cancer biomarkers as well as intriguing new roles of epigenetic regulation in cancer (such as methylation of estrogen receptor in breast cancer patients). This study also uses cell line data to show that COHCAP is capable of analyzing Illumina methylation array and targeted bisulfite sequencing data, with either 1-group or 2-group study designs. The accuracy of COHCAP is accessed using qPCR, EpiTect, and comparison of COHCAP regions of differential methylation with MIRA peaks. This software is freely available at https://sourceforge.net/projects/cohcap/.
COHCAP: an integrative genomic pipeline for single-nucleotide resolution DNA methylation analysis.
Disease, Cell line
View SamplesGenome-wide expression and methylation differences are compared for a normal HCT116 cell line and a derived mutant with altered DNA methylation patterns.
COHCAP: an integrative genomic pipeline for single-nucleotide resolution DNA methylation analysis.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Expression of the PPM1F Gene Is Regulated by Stress and Associated With Anxiety and Depression.
Sex, Age, Specimen part
View SamplesPpm1f regulation in the amygdala after acute stress immobilization
Expression of the PPM1F Gene Is Regulated by Stress and Associated With Anxiety and Depression.
Sex, Age, Specimen part
View SamplesPpm1f regulation in the medial prefrontal cortex (mPFC) after acute stress immobilization
Expression of the PPM1F Gene Is Regulated by Stress and Associated With Anxiety and Depression.
Sex, Age, Specimen part
View SamplesLCM was perfomed on adjacent tumor and stromal cells to identify differentially expressed genes in triple negative breast cancer.
Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection.
No sample metadata fields
View SamplesApoptosis is deregulated in most, if not all, cancers, including hematological malignancies. In this study, we wanted to test whether primary acute myeloid leukemia (AML) samples are sensitive for inhibitor of apoptosis (IAP) protein antagonist treatment in vitro, and which AML subgroup might profit most from such a novel therapeutic strategy. We treated diagnostic samples of 67 adult AML patients with either cytarabine (ara-C) or IAP antagonist BV6 and correlated sensitivity with clinical, cytogenetic and molecular markers, and expression levels of selected genes involved in apoptosis. Primary AML samples showed differential sensitivity to treatment with either ara-C (40% sensitive, 17% intermediate, 43% resistant) or BV6 (51% sensitive, 21% intermediate, 28% resistant). Notably, 69% of ara-C resistant samples showed a good to fair response to IAP inhibition. Furthermore, combination treatment of ara-C with BV6 showed additive effects in most samples. Differences in sensitivity to IAP antagonist treatment correlated with significantly elevated expression levels of TNF and lower levels of XIAP in BV6 sensitive samples, as well as with NPM1 mutations. Gene expression profiling pointed to apoptosis-related pathways, which were specifically induced by IAP inhibition in sensitive samples. Thus, our results suggest IAP inhibition as a potential novel therapeutic option in AML.
Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia.
Sex, Age, Treatment
View Samples