Thymic antigen-presenting cells (APCs), including thymic dendritic cells (t-DCs) and medullary thymic epithelial cells (mTECs) have been described to play a critical role in thymic Treg generation. Our findings could show that both these thymic APCs can induce a more pronounced demethylation of Foxp3 and other Treg-specific epigenetic signature genes in developing Tregs when compared to splenic DCs. In order to elucidate the unique properties of thymic APCs, gene expression profiling was performed in comparison to splenic DCs. Transcriptome analysis of thymic APCs revealed differential expression of costimulatory molecules that could be involved in stable Treg generation. Importantly, both mTEC- and t-DC- induced alloantigen-specific Tregs displayed significantly higher efficacy in prolonging skin allograft acceptance when compared to alloantigen-specific Tregs generated by splenic DCs. Overall design: Thymic APCs, including mTECs and t-DCs and splenic DCs were isolated ex vivo from thymus as CD45-EpCAM+Ly51- (mTECs) and CD45+EpCAM-CD11chiLin- (t-DCs) and from spleen as CD11chiLin- (splenic DCs) (Lin is defined as CD90, CD49b, F4/80 and CD19), respectively.
Unique properties of thymic antigen-presenting cells promote epigenetic imprinting of alloantigen-specific regulatory T cells.
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View SamplesWe investigated at which stage of maturation commitment to a stable Foxp3-expressing phenotype takes place. We assessed stability of Foxp3 expression in thymic Foxp3+ Treg subsets of different maturity, defined by CD24 expression. Next we compared gene expression profiles of Foxp3+ Treg subsets (+) of different maturity (24lo, 24int, 24hi) and could identify a set of genes that were specifically up or downregulated in Foxp3+ Tregs, but not in Foxp3- conventional T cells, in a maturation-dependent manner.
Active demethylation of the Foxp3 locus leads to the generation of stable regulatory T cells within the thymus.
Specimen part
View SamplesThe effect of cyclic mecanical stretch on cardiac gene expression was studied in neonatal rat ventricular myocytes (NRVMs).
Mechanical stretch induced transcriptomic profiles in cardiac myocytes.
Treatment
View SamplesThe rhesus embryonic stem cell line 366.4 differentiates into serotonin neurons. RNA was extracted from ESC colonies, embryoid body (Ebs), Neurospheres in selection (N1), Proliferating serotonin neurons (N2) and differentiating serotonin neurons (N3). RNA was labeled with Enzo biotin labelling kit and hybridized to Rhesus chip from Affymetrix.
Expression profile of differentiating serotonin neurons derived from rhesus embryonic stem cells and comparison to adult serotonin neurons.
Cell line
View SamplesThe aim of this study was to determine how gene expression is changed after arsenite-induced malignant transformation of prostate epithelial cells.
Coordinate H3K9 and DNA methylation silencing of ZNFs in toxicant-induced malignant transformation.
Specimen part, Cell line, Treatment
View SamplesInhibition of miR-361-3p by locked nucleic acid (LNA)/DNA antisense oligonucleotide markedly suppressed the growth of GFP-SAS cells.
MicroRNA-361-3p is a potent therapeutic target for oral squamous cell carcinoma.
Specimen part, Cell line
View SamplesMetastatic colonization involves cancer cell lodgment or adherence in the microvasculature and subsequent migration of those cells across the endothelium into a secondary organ site. To study this process further, we analyzed both in vitro and in vivo migration of human PC-3 prostate cancer cells . We isolated 6 subpopulation of cells: TEM4-18 were isolated from in vitro transendothelial migration of PC-3 cells; GS672.Ug, GS683.LALN and JD1203.Lu are single passaged in vivo cell lines from TEM4-18; GS689.Li and GS694.LAd are twice passaged in vivo cell lines from PC-3 cells. All the subpopulations crossed an endothelial barrier more efficiently and more aggressive in a murine metastatic colonization model than parental PC-3 cells. Microarray and FACS analysis of these cells showed that the expression of many genes previously associated with leukocyte trafficking and cancer cell extravasation were either unchanged or down-regulated. These cells exhibited characteristic molecular markers of an epithelial-to-mesenchymal transition, including frank loss of E-cadherin expression and upregulation of the E-cadherin repressor ZEB1.
Transcriptome-wide landscape of pre-mRNA alternative splicing associated with metastatic colonization.
Cell line
View SamplesCD4+ T lymphocytes are key to immunological memory, but little is known about the lifestyle of memory CD4+ T lymphocytes. We showed that in the memory phase of specific immune responses to antigens, most of the memory CD4+ T lymphocytes relocated into the bone marrow (BM) within 3-8 weeks after their generation, a process involving integrin a2. Antigen-specific memory CD4+ T lymphocytes expressed Ly-6C to a high degree, unlike most splenic CD44hiCD62L- CD4+ T lymphocytes. In adult mice, more than 80% of Ly-6Chi CD44hiCD62L- memory CD4+ T lymphocytes were in the BM. In the BM, they are located next to IL-7-expressing VCAM-1+ stroma cells, and were in a resting state. Upon challenge with antigen, they rapidly expressed cytokines and CD154 and induced the production of high-affinity antibodies, indicating their functional activity in vivo and marking them as professional memory T helper cells
Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow.
Specimen part
View SamplesTo identify novel Peroxisome Proliferator-Activated Receptor gamma (PPARg) responsive secretory and/or transmembrane genes that is related to obesity, we integrated the expression data from the adipose tissue derived from obese mice with the other two data sets: expression profiling of adipocyte differentiation using ST2 cells and siRNA-mediated knockdown of Pparg during ST2 cell adipogenesis.
Fam57b (family with sequence similarity 57, member B), a novel peroxisome proliferator-activated receptor γ target gene that regulates adipogenesis through ceramide synthesis.
Specimen part
View SamplesWe used microarrays to detail transcriptional changes in the rat heart in response to doxorubicin, a chemotherapeutic drug known to induce cardiac disfunction/heart failure
Early effects of doxorubicin in perfused heart: transcriptional profiling reveals inhibition of cellular stress response genes.
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