Hydrogen sulfide (H2S) is an endogenous gasotransmitter and is capable of regulating various endogenous signaling pathways, inculding inflamation and immune response. In mammals, H2S is mainly generated by two pyridoxal-5'-phosphate-dependent enzymes, termed cystathionine -synthase (CBS) and cystathionine -lyase (CSE). CBS-deficient mice showed autoimmune disorders. H2S play important roles in T cell development and differentiation, especially Treg cells development and differentiation.
Hydrogen Sulfide Promotes Tet1- and Tet2-Mediated Foxp3 Demethylation to Drive Regulatory T Cell Differentiation and Maintain Immune Homeostasis.
Specimen part
View SamplesEpidemiological studies have revealed concurrence of specific cancers with other disease states such as metabolic syndrome, inflammatory disease and autoimmune disease. Patients with these chronic conditions have a higher incidence of various cancers, more aggressive tumors, and a higher mortality rate. It has been proposed that obesity, inflammation and chronic disease should be correlated with cancer at the molecular level, but common gene signatures or networks have yet to be described. Here, we identify genes regulated during the process of cellular transformation in both a breast epithelial cell line and a set of isogenic fibroblastic cell lines.
A transcriptional signature and common gene networks link cancer with lipid metabolism and diverse human diseases.
Cell line, Time
View SamplesWe conditionally inactivated mouse Cdx2, a dominant regulator of intestinal development, and mapped its genome occupancy in adult intestinal villi. Although homeotic transformation, observed in Cdx2-null embryos, was absent in mutant adults, gene expression and cell morphology were vitally compromised. Lethality was accelerated in mice lacking both Cdx2 and its homolog Cdx1, with exaggeration of defects in crypt cell replication and enterocyte differentiation. Cdx2 occupancy correlated with hundreds of transcripts that fell but not with equal numbers that rose with Cdx loss, indicating a predominantly activating role at intestinal cis-regulatory regions. Integrated consideration of a mutant phenotype and cistrome hence reveals the continued and distinct requirement in adults of a master developmental regulator that activates tissue-specific genes.
Essential and redundant functions of caudal family proteins in activating adult intestinal genes.
Specimen part
View SamplesWe report the high-throughput profiling of brain RNA from three Drosophila stains: dBRWD3PX2/+, dBRWD3PX2/PX2 and dBRWD3PX2/PX2, yemGS21861/GS21861. By obtaining over 50 million reads of sequence, WE compared the transcriptomic differences among the brains from these three stains. We found that the expression of 871 genes was significantly different between heterozygous control and homozygous dBRWD3 mutant brains (484 upregulated genes, 387 downregulated genes, p<0.05). Gene ontology (GO) analysis of the 871 genes revealed a broad spectrum of biological processes, ranging from synaptic activity to housekeeping metabolism subjective to dBRWD3 regulation. Among the 387 downregulated genes, the expression of 360 genes (92.8%) was increased in the dBRWD3, yem double mutant brains compared with dBRWD3 mutant. Among the 484 upregulated genes, the expression of 412 genes (85.1%) was decreased in the double mutant brains. These differential genes were evenly distributed on X chromosome and autosomes (149 on X, 178 on 2L, 154 on 2R, 166 on 3L, and 207 on 3R). These analyses indicate that dBRWD3 regulates gene expression in the brain mainly through the HIRA/YEM complex. Overall design: Examination of brain transcriptome in 3 Drosophila strains.
Intellectual disability-associated dBRWD3 regulates gene expression through inhibition of HIRA/YEM-mediated chromatin deposition of histone H3.3.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.
Specimen part
View SamplesWe established whether partner transcription factor binding, chromatin structure, or gene expression is compromised upon loss of partner factors cdx2 or hnf4a in mouse intestinal villi
Intestinal master transcription factor CDX2 controls chromatin access for partner transcription factor binding.
Specimen part
View SamplesFollicular T-helper (TFH) cells highly express the programmed cell death-1 (PD-1) molecule. Whereas inhibition of T cell receptor (TCR) signaling and CD28 co-stimulation is thought to be the primary mode of PD-1 functions, how PD-1 regulates TFH development and function remains unclear. Here we show that, when engaged by the ensemble of bystander B cells constitutively expressing PD-1 ligand 1 (PD-L1), PD-1 inhibits T-cell recruitment into follicles. This inhibition involves suppression of PI3K activities downstream of follicle-guidance receptor CXCR5, is independent from co-signaling with the TCR, and necessitates ICOS signaling to overcome. PD-1 further restricts CXCR3 upregulation on TFH cells, serving to concentrate these cells toward the GC territory, where PD-L1-PD-1 interactions between individual TFH and B cells optimize B-cell competition and affinity maturation. Therefore, operating in both costimulation-independent and -dependent manners, PD-1 plays an integral role in orchestrating tissue positioning and function of TFH cells. Overall design: Differential expression analysis between WT and Pdcd1KI/KI CXCR5hi Tfh cells
PD-1 Controls Follicular T Helper Cell Positioning and Function.
Cell line, Treatment, Subject
View SamplesWe generated skeletal muscle-specific knockout mice lacking the transcription factor Yin Yang 1 (YY1) and analyzed expression patterns in the skeletal muscle these mice.
Defective mitochondrial morphology and bioenergetic function in mice lacking the transcription factor Yin Yang 1 in skeletal muscle.
Age, Specimen part
View SamplesFbw7 plays a negative role in pancreatic cancer tumorigenesis and progression. To further clarify the function and mechanism that Fbw7 plays in pancreatic cancer,mRNA microarray assays were performed to identify the genes and signaling pathways that were changed upon Fbw7 overexpression.
FBW7 (F-box and WD Repeat Domain-Containing 7) Negatively Regulates Glucose Metabolism by Targeting the c-Myc/TXNIP (Thioredoxin-Binding Protein) Axis in Pancreatic Cancer.
Cell line, Treatment
View SamplesCell differentiation requires epigenetic modulation of tissue-specific genes and activities of master transcriptional regulators, which are recognized for their dominant control over cellular programs. Using novel epigenomic methods, we characterized enhancer elements specifically modified in differentiating intestinal epithelial cells and found enrichment of transcription factor-binding motifs corresponding to CDX2, a master regulator of the intestine. Directed investigation revealed surprising lability in CDX2 occupancy of the genome, with redistribution from hundreds of sites occupied only in progenitors to thousands of new sites in mature cells. Knockout mice confirmed distinct Cdx2 requirements in dividing and differentiated adult intestinal cells, including responsibility for the active enhancer configuration associated with maturity. Dynamic CDX2 occupancy corresponds with condition-specific gene expression and, importantly, to differential co-occupancy with other tissue-restricted transcription factors: HNF4A in mature cells and GATA6 in progenitors. These results reveal dynamic, context-specific functions and mechanisms of a master transcription factor within a cell lineage.
Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2.
Specimen part, Cell line
View Samples