FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, this protein is specifically expressed by memory B cells (MBCs) and is preferentially localized in subephitelial regions of lymphoid tissues. An expansion of FCRL4+ B cells has been shown in blood or other tissues in various infectious or autoimmune pathologies. In the present work, we generated and characterized in vitro FCRL4+ B cells from purified MBCs using T-dependent and/or T-independent stimulation. FCRL4+ B cells account for 17% of cells generated at day-4 of culture. Transcriptomic and phenotypic analysis of FCRL4+ cells show that they are closely related to FCRL4+ tonsillar MBCs. Interestingly, these cells highly express inhibitory receptors genes as described for exhausted FCRL4+ MBCs in the blood of HIV-viremic individuals. In agreement, in vitro generated FCRL4+ B cells show a significant underexpression of cell cycle genes with a two fold weaker number of cell division compared to FCRL4- cells. Finally, resulting from their reduced proliferation and differentiation potential, we show that FCRL4+ cells are not prone to generate plasma cells, contrary to FCRL4- cells. Given the difficulty to access to in vivo FCRL4+ cells, our in vitro model could be of major interest to study the biology of normal and pathological FCRL4+ cells.
Characterization of human FCRL4-positive B cells.
Specimen part
View SamplesMost cancer deaths are caused by metastases, which are the end-results of circulating tumor cells (CTC) that detach from the cancer primary and succeed to survive in distant organs. The aim of the present study was to develop a gene signature of CTC and to assess its prognostic relevance after surgery for pancreatic ductaladenocarcinoma (PDAC).
Pancreatic cancer circulating tumour cells express a cell motility gene signature that predicts survival after surgery.
Sex, Age, Disease stage
View SamplesFollowing our initial transcriptomic analyses of the male gametophyte development (Honys and Twell, Genome Biol 5:R85, 2004), we identified several candidate genes for the function of transcriptional regulators of the male gametophyte development.
AtbZIP34 is required for Arabidopsis pollen wall patterning and the control of several metabolic pathways in developing pollen.
Specimen part
View SamplesDomestic broiler chickens rapidly accumulate adipose tissue due to intensive genetic selection for rapid growth and are naturally hyperglycemic and insulin resistant, making them an attractive addition to the suite of rodent models used for studies of obesity and type 2 diabetes in humans. Furthermore, chicken adipose tissue is considered as poorly sensitive to insulin and lipolysis is under glucagon control. Excessive fat accumulation is also an economic and environmental concern for the broiler industry due to the loss of feed efficiency and excessive nitrogen wasting, as well as a negative trait for consumers who are increasingly conscious of dietary fat intake. Understanding the control of avian adipose tissue metabolism would both enhance the utility of chicken as a model organism for human obesity and insulin resistance and highlight new approaches to reduce fat deposition in commercial chickens.
Transcriptomic and metabolomic profiling of chicken adipose tissue in response to insulin neutralization and fasting.
Specimen part
View SamplesWe used a smooth muscle cell-specific mineralocorticoid receptor knockout mouse to generate young and aged MR-intact and SMC-MR-KO aortic mRNA to examine the effect of age on vascular mRNA alterations in the presence and absence of SMC-MR.
Smooth Muscle Cell-Mineralocorticoid Receptor as a Mediator of Cardiovascular Stiffness With Aging.
Sex, Specimen part
View SamplesTha altered biological pathways in Epidermolysis bulloda simplex, a rare monogenetic skin disease, have not been well characterized. Thus, the goal of this study is to characterize the expression profile of EBS patients compared with normal subjects using genomic expression analyses. Microarray analyses were performed with RNA isolated from skin biopsies. Robust multiarray analysis (RMA) normalization and Smyths moderated t test were used to select differentially expressed genes. Expression profiling comparisons show that 28 genes are differentially expressed in EBS patients compared to control subjects and 41 genes in EBS-DM compared to their matched controls. Nine genes involved in fatty acid metabolism and 2 genes in epidermal keratinisation are common altered expressed genes between the two subgroups. These two biological pathways contribute both to the formation of the cell envelope barrier and seem to be defective in the severe EBS phenotype. This study demonstrates, for the first time, the relevance of metabolic cluster, specifically fatty acid metabolism in EBS biology. Difference of expression for three (AWAT2, ELOVL , and SPRR4 ) of the five selected genes were validated using real-time reverse transcriptionpolymerase chain reaction. To our knowledge, the distinctive pattern of gene expression that characterizes EBS versus healthy skin tissue has never been reported.
Expression signature of epidermolysis bullosa simplex.
Specimen part, Disease, Disease stage
View SamplesGlobal gene expression patterns were determined from microarray results from sham surgery or following 1 week of plantaris muscle hypertrophy induced by synergist ablation in young adult Pax7-DTA mice (4 months).
Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy.
Age, Specimen part
View SamplesBackground & Aims: HNF4 is an important transcriptional regulator of hepatocyte and pancreatic function. Hnf4 deletion is embryonically lethal with severe defects in visceral endoderm formation, liver maturation and colon development. However, the precise role of this transcription factor in maintaining homeostasis of the adult intestine remains unclear. Herein, we aimed to elucidate the adult intestinal functions of Hnf4. Methods: A conditional intestinal epithelial Hnf4 knockout mouse was generated. Histological abnormality of the colonic mucosa was assessed by immunodetection and Western. Changes in global gene expression and biological network were analyzed. Results: Hnf4 intestine null mice developed normally until reaching young adulthood. Crypt distortion became apparent in the Hnf4 null colon at 3 months of age followed by focal areas of crypt dropout, increased immune cell infiltrates, crypt hyperplasia and early signs of polyposis later in life. A gene profiling analysis identified cell death and cell cycle related to cancer as the most significant sets of genes altered in the Hnf4 colon null mice. Expression levels of the tight junction proteins claudin 4, 8 and 15 were altered early in the colon epithelium of Hnf4 mutants and correlated with increased barrier permeability to a molecular tracer that does not normally penetrate normal mucosa. Conclusion: These observations support a functional role for Hnf4 in protecting the colonic mucosa against the initiation of the changes resembling inflammatory bowel diseases and polyp formation.
Loss of hepatocyte-nuclear-factor-4alpha affects colonic ion transport and causes chronic inflammation resembling inflammatory bowel disease in mice.
No sample metadata fields
View SamplesRegulatory T cells (Tregs) are essential for maintaining proper immune homeostasis. Extracellular signals (e.g. TCR, CD28, IL-2R) are necessary for the generation and maintenance of Tregs, but how these signals are integrated to control the gene expression patterns of Tregs is less clear. Here we show that the epigenetic regulator, Ezh2, was induced by CD28 costimulation and Ezh2 activity was elevated in Tregs as compared to conventional CD4+ T cells. Deletion of Ezh2 in mouse Tregs led to a progressive autoimmune disease because Tregs were compromised after activation, losing proper control of essential Treg lineage genes and adopting a gene expression pattern similar to Foxp3-deficient ‘Tregs.’ Lineage-tracing of Ezh2-deficient Tregs in vivo confirmed that the cells were destabilized selectively in activated Treg populations, which led to a significant loss of Tregs in non-lymphoid tissues. These studies reveal an essential role for Ezh2 in the maintenance of Treg “identity” during cellular activation and differentiation. Overall design: RNAseq of sorted populations of CD62Lhi or CD62Llo Tregs for both Ezh2-HET (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/+ female mice) and Ezh2-KO (Foxp3YFP-Cre/Foxp3WT;Ezh2fl/fl female mice) were generated, in triplicate for each condition, using Illumina HiSeq 2500 single-end 50bp sequencing platform.
The chromatin-modifying enzyme Ezh2 is critical for the maintenance of regulatory T cell identity after activation.
No sample metadata fields
View SamplesPurpose: The goals of this study are to compare transcriptome profiling (RNA-seq) resulting from a Mesp1Cre driven ablation of Hira in the heart at E11.5 and E12.5. Methods: RNA extraction was done in triplicate from Mesp1Cre;Hira-/fl and Mesp1Cre;Hira+/fl embryonic hearts at E11.5 and E12.5 using the QIAGEN RNeasy mini kit. RNAseq was processed by the ICH genomics facility, reads were aligned and normalised using BOWTIE and DEseq R package. Strand NGS 2.5 software was used to re-analyse the aligned files (.bam). By applying the Mann Whitney unpaired test, Benjamini Hochberg False discovery rate (FDR) and filtering the genes using adjusted p-value = 0.05 and absolute fold change = 1.5, 95 % of the results were identical to the DEseq package used by the UCL Genomics facility. Results: We identified 360 coding transcripts changed in the mutant hearts (Mann Whitney unpaired test, Benjamini Hochberg FDR, p = 0.05, FC = 1.5) with no trend towards up- or down-regulation of global transcription (48.8% down vs 51.2% up) at E12.5. Conclusions: This work analyses the role of HIRA in mouse cardiac development. It was found that Tnni2 is the most upregulated gene in the absence of Hira. qRT-PCR validation of 25 targets. Little (<5%) or no variation of fold change between RNAseq and qRT-PCR data were observed. Overall design: Cardiac mRNA profiles of 11-day and 12-day embryonic days Mesp1Cre control (Ctrl) and Mesp1Cre;Hira-/fl (mut) were generated by deep sequencing, in triplicate, using Illumina GAIIx.
HIRA Is Required for Heart Development and Directly Regulates Tnni2 and Tnnt3.
Specimen part, Cell line, Subject
View Samples