The presence of different types of immune cells in adipose tissue has been demonstrated in numerous studies. Whereas cells of the immune system in white adipose tissue contribute to the low-grade chronic inflammation under obese conditions, their function in brown adipose tissue (BAT) remains largely elusive. Here we report a role of regulatory T (Treg) cells in BAT physiology.Ablation of Treg cells resulted in massive invasion of macrophages into BAT concordant with rearrangement of BAT morphology. Treg ablated animals displayed reduced energy expenditure. Our results for the first time demonstrate a functional role of Treg cells in the regulation of energy homeostasis.
Brown adipose tissue harbors a distinct sub-population of regulatory T cells.
Treatment
View SamplesThe transcriptional regulator Rbpj is involved in T-helper (TH) subset polarization, but its function in Treg cells remains unclear. Here we show that Treg-specific Rbpj deletion leads to splenomegaly and lymphadenopathy despite increased numbers of Treg cells with a polyclonal TCR repertoire. A specific defect of Rbpj-deficient Treg cells in controlling TH2 polarization and B cell responses is observed, leading to the spontaneous formation of germinal centers and a TH2-associated immunoglobulin class switch. The observed phenotype is environment-dependent and can be induced by infection with parasitic nematodes. Rbpj-deficient Treg cells adopt open chromatin landscapes and gene expression profiles reminiscent of tissue-derived TH2-polarized Treg cells, with a prevailing footprint of the transcription factor Gata-3. Taken together, our study suggest that Treg cells require Rbpj to specifically restrain TH2 responses, including their own excessive TH2-like differentiation potential. Overall design: We isolated Treg cells from spleens of affected Treg Rbpj-deficient animals and wildtype counterparts. Total RNA was isolated and subjected to gene expression analysis using RNA sequencing
Rbpj expression in regulatory T cells is critical for restraining T<sub>H</sub>2 responses.
Specimen part, Subject
View SamplesThe cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor.
Mesenchymal stem cell features of Ewing tumors.
Specimen part
View SamplesLung alveolarization is a complex process that involves interactions between several cell types and leads to considerable increase in gas-exchange surface area. The step designated secondary septation includes elastogenesis from interstitial fibroblasts.
Gene expression profiling in lung fibroblasts reveals new players in alveolarization.
No sample metadata fields
View SamplesYin Yang 1 (YY1) is a multifunctional zinc-finger-containing transcription factor that plays crucial roles in numerous biological processes by selectively activating or repressing transcription, depending upon promoter contextual differences and specific protein interactions. In mice, Yy1 null mutants die early in gestation while Yy1 hypomorphs die at birth from lung defects. We studied how the epithelial-specific inactivation of Yy1 impacts on lung development. The Yy1 mutation in lung epithelium resulted in neonatal death due to respiratory failure. It impaired tracheal cartilage formation, altered cell differentiation, abrogated lung branching, and caused airway dilation similar to those seen in human congenital cystic lung diseases. The cystic lung phenotype in Yy1 mutants can be explained by the reduced expression of Shh in lung endoderm, a transcriptional target of YY1, and the subsequent derepression of mesenchymal Fgf10 expression. Accordingly, SHH supplementation partially rescued the lung phenotype in vitro. Analysis of human lung tissues revealed decreased YY1 expression in children with pleuropulmonary blastoma (PPB), a rare pediatric lung tumor arising during fetal development and associated with DICER1 mutations. No evidence for a potential genetic interplay between murine Dicer and Yy1 genes during lung morphogenesis was observed. However, the cystic lung phenotype resulting from the epithelial inactivation of Dicer function mimics the Yy1 lung malformations with similar changes in Shh and Fgf10 expression. Together, our data demonstrate the critical requirement for YY1 in lung morphogenesis and identify Yy1 mutant mice as a potential model for studying the genetic basis of PPB.
Epithelial inactivation of Yy1 abrogates lung branching morphogenesis.
Specimen part
View SamplesWe sequenced mRNA from two preparations of isolated Notch-responsive ductal pancreas cells and compared transcript expression to all other non-Notch-responsive cells from each sample to charactarize zebrafish centroacinar cells. Overall design: Determination of gene expression levels in centroacinar cells and non-centroacinar cells from adult pancreas.
Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration.
No sample metadata fields
View SamplesForty-four paired (from the same patient) samples of head and neck squamous cell carcinoma (HNSCC) and normal tissue were studied with Affymetrix U95A chips. A stringent multi-test approach, combining 7 traditional and microarray-specific statistical tests, was used to analyze the resultant data. Candidate genes were assigned to tiers of significance based on the number of statistical tests that each gene satisfied. Representative genes (both up-regulated and down-regulated) from each of the 3 tiers would be quantified with RT-PCR on both microarray-tested and new samples of HNSCC.
Selection and validation of differentially expressed genes in head and neck cancer.
No sample metadata fields
View SamplesPolycomb-group proteins form multimeric protein complexes involved in transcriptional silencing. The Polycomb Repressive complex 2 (PRC2) contains the Suppressor of Zeste-12 protein (Suz12) and the histone methyltransferase Enhancer of Zeste protein-2 (Ezh2). This complex, catalyzing the di- and tri-methylation of histone H3 lysine 27, is essential for embryonic development and stem cell renewal. However, the role of Polycomb-group protein complexes in the control of the intestinal epithelial cell (IEC) phenotype is not known. We investigated the impact of Suz 12 depletion on gene expression in IEC-6 cells.
The histone H3K27 methylation mark regulates intestinal epithelial cell density-dependent proliferation and the inflammatory response.
Cell line
View SamplesDespite advances in Hodgkin lymphoma (HL) treatment, about 20% of patients still die due to progressive disease. Current prognostic models predict treatment outcome with imperfect accuracy, and clinically relevant biomarkers are yet to be established that improve upon the International Prognostic Scoring (IPS) system. We analyzed 130 frozen diagnostic lymph node biopsies from classical HL patients by gene expression profiling to describe cellular signatures correlated with treatment outcome.
Tumor-associated macrophages and survival in classic Hodgkin's lymphoma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThe C57BL/6.NOD-Aec1Aec2 mouse is a model for primary Sjgrens syndrome and was constructed by introducing two genetic intervals derived from the NOD mouse that confers Sjgrens syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice.
Transcriptional landscapes of emerging autoimmunity: transient aberrations in the targeted tissue's extracellular milieu precede immune responses in Sjögren's syndrome.
Sex, Age, Specimen part
View Samples