The goal of the study is a high-throughput evaluation of the effect of TGFb treatment on gene expression.
Resolving the Combinatorial Complexity of Smad Protein Complex Formation and Its Link to Gene Expression.
Specimen part
View SamplesPancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures in PDAC. Here we show that transcriptional co-factor Transducin beta-like (TBL) 1 was over-expressed in both human and murine PDAC. Inactivation of TBL1 in human and mouse pancreatic cancer cells reduced cellular proliferation and enhanced chemosensitivity, correlating with diminished glucose uptake, glycolytic flux, and PI3kinase signaling. TBL1 deficiency both prevented and reversed pancreatic tumor growth in mice, triggering transcriptional PI3kinase inhibition also in vivo. As TBL1 mRNA levels were also found to correlate with overall and disease-free survival in a cohort of human PDAC patients and to predict therapy responsiveness in these subjects, TBL1 expression may serve both as a novel prognostic marker and molecular target in the treatment of human PDAC.
Transcriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy.
Cell line, Treatment
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: 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 SamplesLamina propria and muscularis macrophages, were sorted at steady steate and 2h after oral exposure to an attenuated form of Salmonella, comparison among these populations showed that the muscularis macrophages quckly respond to the presence of intestinal bacteria, upregulating some important tissue protective genes. Overall design: intestinal macrophages from 3 mice were pooled into one RNA sample, the experiment was done control X infected and was repeated twice
Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.
Specimen part
View SamplesCD4+ T cells differentiate into phenotypically distinct T-helper cells upon antigenic stimulation. Regulation of plasticity between these CD4+ T-cell lineages is critical for immune homeostasis and prevention of autoimmune diseases. However, the factors that regulate lineage stability are largely unknown. Here we investigate a role for retinoic acid (RA) in the regulation of lineage stability using T helper 1 (Th1) cells, traditionally considered the most phenotypically stable Th subset. We found that RA, through its receptor RARa, sustains stable expression of Th1 lineage specifying genes as well as repressing genes that instruct Th17 cell fate. RA signaling is essential for limiting Th1 cell conversion into Th17 effectors and for preventing pathogenic Th17 responses in vivo. Our studies identify RA-RARa as a key component of the regulatory network governing Th1 cell fate and define a new paradigm for the development of pathogenic Th17 cells. These findings have important implications for autoimmune diseases in which dysregulated Th1-Th17 responses are observed.
Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.
No sample metadata fields
View SamplesWe show that the epididymal white adipose tissue harbors 4 subpopulations of macrophages (VAM1, VAM2, PreVAM and DPs), 2 subpopulations of Dendritic Cells (CD11B+CD103- and CD11B-CD103+) and monocytes. VAMs display a gene signature enriched in pathways related to anti-inflammatory/ detoxifying and repair processes. Our gene expression work shows no evidence of an M2 to a Classically Activated/M1 shift during diet-induced obesity (DIO). Gene expression of VAMs or DP macrophages cannot be defined as M1 or M1-like. Our data are more compatible with the category of “Metabolically-activated” macrophages (MMe) Overall design: Examination of RNA expression changes in different epididymal adipose tissue myeloid subpopulations in lean versus obese animals harboring metabolic syndrome
Vasculature-associated fat macrophages readily adapt to inflammatory and metabolic challenges.
Cell line, Subject
View SamplesWe investigated transcriptional changes in CD4CD8aa and CD4 intraepthelial lymphocytes.
Transcriptional reprogramming of mature CD4⁺ helper T cells generates distinct MHC class II-restricted cytotoxic T lymphocytes.
Specimen part
View SamplesAffymetrix microarrays were used to determine the mRNA composition of mRNPs obtained by immunoprecipitation with IRP1 (iron regulatory protein 1).
Identification of target mRNAs of regulatory RNA-binding proteins using mRNP immunopurification and microarrays.
Sex
View Samples