Acquisition of effector properties is a key step in the generation of cytotoxic T lymphocytes (CTLs). Here we show that inflammatory signals regulate Dicer expression in CTL, and that deletion or depletion of Dicer in mouse or human activated CD8+ T cells causes upregulation of perforin, granzyme and effector cytokines. Genome-wide analysis of miRNA changes induced by exposure of differentiating CTLs to IL-2 and inflammatory signals identifies miR-139 and miR-150 as components of a miRNA network that controls perforin, eomesodermin (Eomes) and IL-2Ra expression in differentiating CTLs and whose activity is modulated by IL-2, inflammation and antigenic stimulation. Overall our data show that strong IL-2R and inflammatory signals act through Dicer and miRNAs to control the cytolytic program and other aspects of effector CTL differentiation. Overall design: Comparison of control and Dicer knock-out CTLs differentiated in vitro; Comparison of wild type CTLs differentiated in vitro with or without inflammatory stimuli; Comparison of effector and memory precursor CTLs isolated from mice infected with LCMV-Armstrong
MicroRNA-directed program of cytotoxic CD8+ T-cell differentiation.
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View SamplesA randomized, open-label, multicenter, phase II trial (NCT00455533) enrolled previously untreated women with histologically-confirmed primary invasive breast adenocarcinoma (T23, N03, M0, tumor size 2.0 cm), regardless of hormone receptor or HER2 expression status. Patients received sequential neoadjuvant therapy starting with 4 cycles of AC (doxorubicin 60 mg/m2 intravenously and cyclophosphamide 600 mg/m2 intravenously) given every 3 weeks, followed by 1:1 randomization to either ixabepilone (40 mg/m2 3-hour infusion) every 3 weeks for 4 cycles, or paclitaxel (80 mg/m2 1-hour infusion) weekly for 12 weeks.
Biomarker analysis of neoadjuvant doxorubicin/cyclophosphamide followed by ixabepilone or Paclitaxel in early-stage breast cancer.
Sex, Age
View SamplesDetailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice.
Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress.
Age, Specimen part, Treatment
View SamplesTo assess the mechanism by which adult germ cells induce cbs-1 expression in the intestine at cold temperature, we performed transcriptome analysis of extruded germ lines from wild-type worms upon iff-1 knockdown or temperature increase Overall design: We extruded germ line of iff-1 RNAi-treated worms at 15°C and empty vector (EV) RNAi-treated worms at 20°C and compared to the germ line of EV RNAi-treated worms at 15°C.
Prostaglandin signals from adult germ stem cells delay somatic aging of <i>Caenorhabditis elegans</i>.
Specimen part, Subject
View SamplesMany tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRß signaling. By screening a secretome library, we found that the human immunoreceptor NKp44 encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of IFN-? and TNF-a that induced tumor cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumor cell cycle genes correlated with NCR2 and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumors expressing PDGF-DD more effectively than control mice, an effect enhanced by blockade of the inhibitory receptor CD96 or CpG-oligonucleotide treatment. Thus, whilst cancer cell production of PDGF-DD supports tumor growth and stromal reaction, it concomitantly activates innate immune responses to tumor expansion. Overall design: RNAseq of NK cell and tumor cell samples in reponse to various stimuli
Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor.
Specimen part, Cell line, Treatment, Subject
View SamplesThe effect of PDGF-DD on the gene expression of human tonsil ILC1 is unknown. We used microarray to determine the transcriptional differences between unstimulated and PDGF-DD-stimulated human tonsil ILC1.
Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor.
Specimen part
View SamplesThe development of complex tissues requires that mitotic progenitor cells integrate information from the environment. The highly varied outcomes of such integration processes undoubtedly depend at least in part upon variations among the gene expression programs of individual progenitor cells. To date, there has not been a comprehensive examination of these differences among progenitor cells of a particular tissue. Here, we used comprehensive gene expression profiling to define these differences among individual progenitor cells of the vertebrate retina. Retinal progenitor cells (RPCs) have been shown by lineage analysis to be multipotent throughout development and to produce distinct types of daughter cells in a temporal, conserved order. A total of 42 single RPCs were profiled on Affymetrix arrays. An extensive amount of heterogeneity in gene expression among RPCs, even among cells isolated from the same developmental time point, was observed. While many classes of genes displayed heterogeneity of gene expression, the expression of transcription factors constituted a significant amount of the observed heterogeneity. Additionally, the expression of cell cycle related transcripts showed differences among those associated with G2 and M, versus G1 and S phase, suggesting different levels of regulation for these genes. These data provide insights into the types of processes and genes that are fundamental to cell fate choices, proliferation decisions, and, for cells of the central nervous system, the underpinnings of the formation of complex circuitry.
Individual retinal progenitor cells display extensive heterogeneity of gene expression.
Specimen part
View SamplesWe used oligonucleotide microarrays to address the specificities of transcriptional responses of adult Drosophila to different stresses induced by paraquat and H2O2, two oxidative stressors, and by tunicamycin which induces an endoplasmic reticulum (ER) stress. Flies were tested 24 hours after exposure to continuous stresses induced by ingestion of paraquat, H2O2 or tunicamycin at concentrations leading to similar effects on viability. We used concentrations of 1% H2O2, 5mM paraquat and 12uM of tunicamycin which lead to negligeable mortality at 24 hours. A paraquat concentration of 15mM was also used for comparison with previous studies Both specific and common responses to the three stressors were observed and whole genome functional analysis identified several important classes of stress responsive genes. Within some functional classes, we observed large variabilities of transcriptional changes between isozymes, which may reflect unsuspected functional specificities.
Genome wide analysis of common and specific stress responses in adult drosophila melanogaster.
Sex, Age, Compound, Time
View SamplesAnalysis of whole heart samples from Hdac3-Isl1KO embryos at embryonic day E9.5. Results provide insights into the role of Hdac3 in second heart field-derived cardiac cells.
Histone Deacetylase 3 Coordinates Deacetylase-independent Epigenetic Silencing of Transforming Growth Factor-β1 (TGF-β1) to Orchestrate Second Heart Field Development.
Specimen part
View SamplesIdentification of genes expressed in a preferential manner in the developing ciliary body/iris will provide a starting point for future functional analyses. To identify candidate genes expressed in a variety of ocular tissues during development, we have profiled single cells from the developing eye. Post hoc identification of the origin of these cells showed that they included cells from the periphery of the developing optic cup. By comparing the expression profiles of these cells to many retinal cell types, candidate genes for preferential expression in the periphery were identified.
Identification of genes expressed preferentially in the developing peripheral margin of the optic cup.
Specimen part
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