The transcription factor STAT1 is essential for interferon- (IFN) mediated protective immunity in humans and mice. Two splice isoforms of STAT1, STAT1 and STAT1, differ with regard to a C-terminal transactivation domain, which is absent in STAT1. Dimers of STAT1 are therefore considered transcriptionally inactive and potential competitive inhibitors of STAT1. Contrasting this view, generation and analysis of mice deficient for either STAT1 or STAT1 demonstrated transcriptional activity of the STAT1 isoform and its enhancement of innate immunity. Gene expression profiling in primary cells revealed overlapping, but also non-redundant and gene-specific activities of STAT1 and STAT1 in response to IFN. Consistently, both isoforms mediated protective, IFN-dependent immunity against the bacterium Listeria monocytogenes, although with remarkably different efficiency. In contrast, STAT1 and STAT1 were largely redundant for transcriptional responses to IFN/ and for IFN/-dependent antiviral activity. Collectively, our data shed new light on how STAT1 isoforms contribute to antimicrobial immunity.
STAT1β is not dominant negative and is capable of contributing to gamma interferon-dependent innate immunity.
Specimen part
View SamplesThe tissue of origin form metastatic tumors is sometimes difficult to identify from clinical and histologic information. Gene expression signatures are one potential method for identifying the tissue of origin. In the development of algorithms to identify tissue of origin, a collection of human tumor metastatic specimens with known primary sites or primary tumors with poor differentiation are very useful in identifying gene expressions signatures that can classify unknown specimens as to the tissue of origin. Here we describe a series of 276 such tumor specimens used for this purpose. The specimens are poorly differentiated, undifferentiated and metastatic specimens from tumors of the following types/tissues of origin: breast, liver, non-Hodgkin's lymphoma, non-small cell lung cancer, ovary, testicular germ cell, thyroid, kidney, pancreas, colorectal cancer, soft tissue sarcoma, bladder, gastric cancer, prostate and melanoma. This data combined with other series (GSE2109) was used to validate a proprietary tumor classification algorithm of Pathwork Diagnostics. The results of this validation set (N = 545 CEL files) showed that the algorithm correctly identified the tissue of origin for 89.4% of the specimens.
Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin.
Sex, Age
View SamplesBP and ER encode proteins that act synergistically to regulate Arabidopsis inflorescence architecture. To search for genes/proteins that influence the BP/ER signaling pathways, we conducted mutagenesis of the bp er double mutant and found that a mutation in FILAMENTOUS FLOWER (FIL) suppresses many of the morphological/developmental defects in bp er. Given that FIL encodes a Zn-finger containing transcription factor, microarray analysis was conducted on bp er vs. the bp er fil line to identify genes that are misregulated and which might implicate specific genes/proteins/pathways that are involved in regulating inflorescence development.
A novel Filamentous Flower mutant suppresses brevipedicellus developmental defects and modulates glucosinolate and auxin levels.
No sample metadata fields
View SamplesVaried genes may be responsible for the functional differences of distinct subsets of T cells. As a result, it is possible that regulatory T cells and pathogenic T cells may display a different set of gene profile regulating their functional status.
Killer cell Ig-like receptor (KIR) 3DL1 down-regulation enhances inhibition of type 1 diabetes by autoantigen-specific regulatory T cells.
Specimen part
View SamplesDirect reprogramming of human fibroblasts to a pluripotent state has been achieved through ectopic expression of the transcription factors OCT4, SOX2, and either cMYC and KLF4 or NANOG and LIN28. Little is known, however, about the mechanisms by which reprogramming occurs, which is in part limited by the low efficiency of conversion. To this end, we sought to create a doxycycline-inducible lentiviral system to convert primary human fibroblasts and keratinocytes into human induced pluripotent stem (hiPS) cells. hiPS cells generated with this system were molecularly and functionally similar to human embryonic stem (hES) cells, demonstrated by gene expression profiles, DNA methylation status, and differentiation potential. While expression of the viral transgenes was required for several weeks in fibroblasts, we found that 10 days was sufficient for the reprogramming of keratinocytes, suggesting that the kinetics of reprogramming are cell-type dependent. Using our inducible system, we developed a strategy to induce hiPS cell formation at high frequency by generating differentiated cells that contain the viral transgenes in a pattern that enables successful induction of pluripotency. Upon addition of doxycycline to differentiated hiPS-derived cells, we obtained secondary hiPS cells at a frequency at least 100-fold greater than the initial conversion. The ability to reprogram cells with high efficiency provides a unique platform to dissect the underlying molecular and biochemical processes that accompany nuclear reprogramming.
A high-efficiency system for the generation and study of human induced pluripotent stem cells.
No sample metadata fields
View Samplesß1-integrin is the major ß-integrin subunit expressed in both lens epithelial and fiber cells. Our previous research indicated that ß1-integrin is essential for the maintenance of lens epithelial integrity and survival in late embryonic lens development (Simirskii et al, 2009). Lack of ß1-integrin in the lens will lead to severe micropthalmia and lack of lens in adult mice. In order to study the mechanisms involved, high throughput RNA sequencing (RNAseq) was performed to determine the genes that are differentially expressed between E15.5 wild type (WT) lenses and lenses that lack ß1-integrin expression due to the action of MLR10 CRE (ß1-cKO). The methodology used here is similar to the other RNAseq experiments that were previously performed in our lab (Manthey et al., 2014a and Audette et al, 2015) (Geo accession: GSE 49949 and GSE69940) . Meanwhile, the filtering criteria and processing procedures were also published (Manthey et al., 2014b). Compared to WT, 120 genes were found to be differentially expressed in ß1-cKO lenses. Moreover, bioinformatics tools (DAVID (the database for Annotation, Visulization and Integrated Discovery), and PANTHER (Protein Analysis through Evolutionary Relationship) classification system) as well as manual literature searching was applied for further data analysis. It showed that genes involved in EMT and stress-responses were differentially expressed in ß1-cKO compared to that of WT. Description of filtering criteria: To identify the differentially expressed genes, pair-wise qCML method exact tests with a Benjamini Hochberg false discovery rate correction greater than the threshold of P<0.05 was applied, which identified 5120 genes. As previously described (Manthey et al., 2014b), most of the genes differentially expressed between inbred C57Bl/6 <har> and mice with a mixed background were below a threshold of 2.5 fold change. Therefore, all differentially expressed genes with a less than 2.5 fold change were filtered out. Further, genes whose expression level were not high enough to be biologically significant were also filtered out, based on the RPMK (Reads per Kilobase per million reads) value. Any gene in the final list has RPKM greater that 2 in either WT or ß1-cKO samples, a value that corresponds to approximately 1 mRNA molecule per cell. By applying a combination of these filtering criteria, 120 differentially expressed genes were found, which could potentially elucidate the molecular connections between conditional deletion of ß1-intergrin from the lens and the observed phenotypic abnormalities. Manthey, A. L., Lachke, S. A., FitzGerald, P. G., Mason, R. W., Scheiblin, D. A., McDonald, J. H. and Duncan, M. K. (2014a) ''Loss of Sip1 leads to migration defects and retention of ectodermal markers during lens development'', Mech Dev 131: 86-110. Manthey, A. L., Terrell, A. M., Lachke, S. A., Polson, S. W. and Duncan, M. K. (2014b) ''Development of novel filtering criteria to analyze RNA-sequencing data obtained from the murine ocular lens during embryogenesis'', Genom Data 2: 369-374. Overall design: RNA-Seq comparison of C57Bl/6 <har> wild type controls and ß1-integrin conditional knockout lenses at E15.5, three biological replicates were used in each group
β1-Integrin Deletion From the Lens Activates Cellular Stress Responses Leading to Apoptosis and Fibrosis.
Specimen part, Subject
View SamplesPurpose: Next-generation sequencing (NGS) has been used to study the gene expression in different samples under air and ethylene treatment. The goal of this study is to uncover how ENAP1 and H3K23Ac dynamically coordinate with EIN3 to regulate gene expression in response to ethylene. Overall design: Whole seedling mRNA profiles of 3-day old ein2, ein3eil1, ENAP1ox/ein2 and ENAP1ox/ein3eil1 (in COL background) were generated by sequencing, in 2 replications, using Illumina HiSeq 2000
EIN2 mediates direct regulation of histone acetylation in the ethylene response.
Specimen part, Subject
View SamplesThe identification of gene regulatory modules is an important yet challenging problem in computational biology. While many computational methods have been proposed to identify regulatory modules, their initial success is largely compromised by a high rate of false positives, especially when applied to human cancer studies. New strategies are needed for reliable regulatory module identification.
Multilevel support vector regression analysis to identify condition-specific regulatory networks.
Sex, Age, Cell line, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Endogenous mammalian histone H3.3 exhibits chromatin-related functions during development.
Specimen part
View SamplesMature seeds of Arabidopsis thaliana are desiccation tolerant, but they lose DT while progressing to germination. Yet, there is a small developmental window during which DT can be rescued by treatment with abscisic acid (ABA).
A gene co-expression network predicts functional genes controlling the re-establishment of desiccation tolerance in germinated Arabidopsis thaliana seeds.
No sample metadata fields
View Samples