This experiment was a time course performed over 24 hours to look at the effects on gene expression of exposure to low red:far-red ratio light in Arabidopsis thaliana plants. In this way genes involved in the shade avoidance response might be identified. This experiment was designed for gene identification only and containes no replicates,genes identified were verified by quantitative PCR for publication.
Gating of the rapid shade-avoidance response by the circadian clock in plants.
Specimen part, Disease, Disease stage, Subject
View SamplesThe adoptive transfer of chimeric antigen receptor- (CAR) modified T cells is revolutionizing the treatment of B cell malignancies and has the potential to be applied to other diseases. CARs redirect T cell specificity by linking an antigen recognition domain to T cell signaling modules comprised of CD3z to provide signal 1, and CD28 or 4-1BB to provide costimulation. CD28/CD3z and 4-1BB/CD3z CARs confer differences in effector function and cell fate that affect clinical efficacy and toxicity. These differences may result from activation of divergent transcriptional programs. To gain this insight, we analyzed changes in gene expression in stimulated and resting CD28/CD3z or 4-1BB/CD3z CAR T cells. CD28/CD3z CAR stimulation initiated more marked early transcriptional changes with greater fold increases in the expression of effector molecules including GZMB, IFNG, IL2, TNF, and IL6. Direct comparison of CD28/CD3z and 4-1BB/CD3z samples stimulated for 6 hours identified 1,673 differentially expressed genes. Of these, the memory T cell-associated genes KLF2, IL7R, and FAM65B were expressed at lower levels in CD28/CD3z CAR T cells. KLF2 and IL7R are FOXO transcription factor family targets and we found that FOXO4 expression was similarly reduced in CD28/CD3z CAR T cells. CD28/CD3z CAR stimulation induces an effector T cell-like transcriptional profile that may underlie the decreased persistence and increased risks of toxicities observed with CD28/CD3z CAR T cells in early clinical trials. Overall design: Purified CD28/CD3z and 4-1BB/CD3z CAR T cells were prepared from healthy donors and stimulated by incubation with anti-CAR beads, or left unstimulated by incubation with control beads. Total RNA was harvested 6 or 24 hours after treatment. Three biological replicates for each treatment condition were prepared, yielding 24 total samples for analysis. A42 and A44 denote 4-1BB/CD3z CARs, A43 and A45 denote CD28/CD3z CARs.
Phosphoproteomic analysis of chimeric antigen receptor signaling reveals kinetic and quantitative differences that affect cell function.
Subject, Time
View SamplesAbstract: Alternative splicing (AS) plays a major role in the generation of proteomic diversity and in gene regulation. However, the role of the basal splicing machinery in regulating AS remains poorly understood. Here we show that the core snRNP protein SmB/B’ self-regulates its expression by promoting the inclusion of a highly-conserved alternative exon in its own pre-mRNA that targets the spliced transcript for nonsense-mediated mRNA decay (NMD). Depletion of SmB/B’ in human cells results in reduced levels of snRNPs and in a striking reduction in the inclusion levels of hundreds of alternative exons, with comparatively few effects on constitutive exon splicing levels. The affected alternative exons are enriched in genes encoding RNA processing and other RNA binding factors, and a subset of these exons also regulate gene expression by activating NMD. Our results thus demonstrate a role for the core spliceosomal machinery in controlling an exon network that appears to modulate the levels of many RNA processing factors. Overall design: HeLa cells were transfected with a control non-targeting siRNA pool (siNT), or with siRNA pools designed to knockdown SmB/B'' or SRSF1 (also known as SF2/ASF/SFRS1). Sequence reads were aligned to exon-exon junction sequences in a database of EST/cDNA-mined cassette-type alternative splicing events. Processed data files (.bed and .txt) provided as supplementary files on the Series record. Processed data file build information: hg18.
Regulation of alternative splicing by the core spliceosomal machinery.
No sample metadata fields
View SamplesTumors that show evidence of epithelial to mesenchymal transition (EMT) have been associated with metastasis, drug resistance, and poor prognosis. EMT may alter the molecular requirements for growth and survival in different contexts, but the underlying mechanisms remain incomplete. Given the heterogeneity along the EMT spectrum between and within tumors it is important to define the requirements for growth and survival in cells with an epithelial or mesenchymal phenotype to maximize therapeutic efficacy.
Epithelial-to-mesenchymal transition rewires the molecular path to PI3K-dependent proliferation.
Specimen part, Cell line, Treatment
View SamplesOBJECTIVE: Acromegaly is a rare endocrine disorder with excess growth hormone (GH) production. This disorder has important metabolic effects in insulin resistance and lipolysis. The objective of this study was to explore transcriptional changes induced by GH in adipose tissue. METHODS: The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex-vivo for lipolysis and ceramide levels. Adipose tissue was analyzed by RNA sequencing (RNA-seq). RESULTS: There was evidence of reduced insulin sensitivity based on the increase in fasting glucose, insulin and HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3) as well as several novel transcriptional changes, some of which may be important for GH signal regulation (PTPN3 and PTPN4) and the effect of GH on growth and proliferation. Several transcripts could potentially be important in GH-induced metabolic changes. Specifically, induction of LPL, ABHD5, and ACVR1C could contribute to enhanced lipolysis and may explain the suggestive enhancement of adipose tissue lipolysis in acromegaly patients as reflected by glycerol release from the explants of the two groups of patients (p=0.09). Higher expression of SCD and TCF7L2 could contribute to insulin resistance. Expression of HSD11B1 was reduced and GR was increased, predicting modified glucocorticoid activity in acromegaly. CONCLUSIONS: We identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. Overall design: DESIGN: Patients with acromegaly (n=9) or non-functioning pituitary adenoma (n=11) were prospectively observed from March 2011 to June 2012. Sequencing was performed on RNA from 7 acromegaly patients and 11 controls.
Gene Expression Signature in Adipose Tissue of Acromegaly Patients.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The bHLH transcription factor POPEYE regulates response to iron deficiency in Arabidopsis roots.
Age, Specimen part
View SamplesTranscriptional profile of whole roots of wild-type and pye-1 mutants exposed to 24 hours -Fe were generated
The bHLH transcription factor POPEYE regulates response to iron deficiency in Arabidopsis roots.
Age, Specimen part
View SamplesPericycle specific transcriptional profiles were generated by FACS (Fluorescence Activated Cell Sorting) of roots that express a pericycle-specific GFP-reporter. FACS cell populations were isolated from roots grown under standard conditions or roots that had been transferred to -Fe media for 24 hours.
The bHLH transcription factor POPEYE regulates response to iron deficiency in Arabidopsis roots.
Age, Specimen part
View SamplesBackground:
Natural variants of AtHKT1 enhance Na+ accumulation in two wild populations of Arabidopsis.
Specimen part
View SamplesWe wanted to understand at what level BTS acts, i.e. how upstream BTS acts and if BTS misregulation affets only a subset or multiple subsets of Fe regulated genes. We studied WT and bts-3 mutant roots.
BRUTUS and its paralogs, BTS LIKE1 and BTS LIKE2, encode important negative regulators of the iron deficiency response in Arabidopsis thaliana.
Specimen part
View Samples