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GSE22707
Homo sapiens
65 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transplant recipients spontaneously accepting their grafts in the absence of immunosuppression demonstrate the feasibility of attaining allograft tolerance in humans. Previous studies have identified blood transcriptional and cell phenotypic markers specific for either liver or kidney tolerant recipients, but the two settings have not been directly compared yet employing the same platforms. To identify potential similarities in immune parameters between recipients tolerant to different organs, we analyzed blood samples from tolerant and non-tolerant liver and kidney recipients employing whole genome expression microarrays. Tolerant and non-tolerant liver and kidney recipients differed in their peripheral blood expression patterns, but no significant overlap was observed between the two datasets. This was confirmed at the functional level by employing gene set enrichment analysis.The lack of obvious similarities in immune parameters associated with liver and kidney tolerant recipients implies the involvement of different mechanisms in the two settings and argues against the existence of a common immunological constant of spontaneous operational tolerance in clinical transplantation.
Publication Title
Comparison of transcriptional and blood cell-phenotypic markers between operationally tolerant liver and kidney recipients.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Due to its low level of nephrotoxicity and capacity to harness tolerogenic pathways, sirolimus (SRL) has been proposed as an alternative to calcineurin inhibitors in transplantation. The exact mechanisms underlying its unique immunosuppressive profile in humans, however, are still not well understood. In the current study we aimed to depict the in vivo effects of SRL in comparison with cyclosporin A (CSA) by employing gene expression profiling and multiparameter flow cytometry on blood cells collected from stable kidney recipients under immunosuppressant monotherapy. SRL recipients displayed an increased frequency of CD4+CD25highFoxp3+ T cells. However, this was accompanied by an increased number of effector memory T cells and by enrichment in NFkB-related pro-inflammatory expression pathways and monocyte and NK cell lineage-specific transcripts. Furthermore, measurement of a transcriptional signature characteristic of operationally tolerant kidney recipients failed to detect differences between SRL and CSA treated recipients. In conclusion, we show here that the blood transcriptional profile induced by SRL monotherapy in vivo does not resemble that of operationally tolerant recipients and is dominated by innate immune cells and NFkB-related pro-inflammatory events. These data provide novel insights on the complex effects of SLR on the immune system in clinical transplantation.
Publication Title
Comparative transcriptional and phenotypic peripheral blood analysis of kidney recipients under cyclosporin A or sirolimus monotherapy.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
mmunosuppressive drugs can be completely withdrawn in up to 20% of liver transplant recipients, commonly referred to as operationally tolerant. Immune characterization of these patients, however, has not been performed in detail, and we lack tests capable of identifying tolerant patients among recipients receiving maintenance immunosuppression. In the current study we have analyzed a variety of biological traits in peripheral blood of operationally tolerant liver recipients in an attempt to define a multiparameter fingerprint of tolerance. Thus, we have performed peripheral blood gene expression profiling and extensive blood cell immunophenotyping on 16 operationally tolerant liver recipients, 16 recipients requiring on-going immunosuppressive therapy, and 10 healthy individuals. Microarray profiling identified a gene expression signature that could discriminate tolerant recipients from immunosuppression-dependent patients with high accuracy. This signature included genes encoding for ?d T-cell and NK receptors, and for proteins involved in cell proliferation arrest. In addition, tolerant recipients exhibited significantly greater numbers of circulating potentially regulatory T-cell subsets (CD4+CD25+ T-cells and Vd1+ T cells) than either non-tolerant patients or healthy individuals. Our data provide novel mechanistic insight on liver allograft operational tolerance, and constitute a first step in the search for a non-invasive diagnostic signature capable of predicting tolerance before undergoing drug weaning.
Publication Title
Multiparameter immune profiling of operational tolerance in liver transplantation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pericytes derived from skin dermis can substantially enhance the short-term tissue-regenerative capacity of human epidermal cells already committed to differentiation; they also display both phenotypic and functional properties of mesenchymal stem cells. In this microarray analysis, we compared the gene expression profile of dermal pericytes to that of the remaining dermal cells of neonatal human foreskin.
Publication Title
A role for pericytes as microenvironmental regulators of human skin tissue regeneration.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Analysis of estrogen receptor (ER)-positive MCF7 cell total RNA expression and polysome-assiciated RNA expression following treatment with estradiol (E2) and vehicle (etoh).
Publication Title
Estrogen coordinates translation and transcription, revealing a role for NRSF in human breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 2 Downloadable Samples
- Affymetrix Arabidopsis Genome Array (ag)
Description
T2 progenies of two transgenic lines overexpressing ERF transcription factor WIN1 were grown on soil in parallel under identical conditions. mRNA was extracted from pooled leaves from multiple plants of each line for the microarray experiement.
Publication Title
WIN1, a transcriptional activator of epidermal wax accumulation in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The objective of the study was to better understand the mechanism behind scar formation by identifying ECM factors and other unique genes differentially expressed during rat ligament healing via microarray. Rat medial collateral ligaments (MCL) were surgically transected or left intact. MCLs were collected at day 3 or 7 post-injury and used for microarray analysis. Results were compared to the normal intact ligaments.
Publication Title
Gene profiling of the rat medial collateral ligament during early healing using microarray analysis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Saccharomyces cerevisiae
- 83 Downloadable Samples
Illumina HiSeq 2500, Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
Purpose: The ability to rationally manipulate the transcriptional states of cells would be of great use in medicine and bioengineering. We have developed a novel algorithm, NetSurgeon, which utilizes genome-wide gene regulatory networks to identify interventions that force a cell toward a desired expression state. Results: We used NetSurgeon to select transcription factor deletions aimed at improving ethanol production in S. cerevisiae cultures that are catabolizing xylose. We reasoned that interventions that move the transcriptional states of cells utilizing xylose toward the fermentative state typical of cells that are producing ethanol rapidly (while utilizing glucose) might improve xylose fermentation. Some of the interventions selected by NetSurgeon successfully promoted a fermentative transcriptional state in the absence of glucose, resulting in strains with a 2.7-fold increase in xylose import rates, a 4-fold improvement in xylose integration into central carbon metabolism, or a 1.3-fold increase in ethanol production rate. Conclusions: We conclude by presenting an integrated model of transcriptional regulation and metabolic flux that will enable future metabolic engineering efforts aimed at improving xylose fermentation to prioritize functional regulators of central carbon metabolism. Overall design: Mutant and wildtype S. cerevisiae cells were put into 48 hour aerobic batch fermentations of synthetic complete medium supplmented with 2% glucose and 5% xylose and culture samples were taken at 4 hours and 24 hours for transcriptional profiling performed by RNA-Seq analysis. In addition, wildtype S. cerevisiae cells were grown in various single carbon sources for 12 hours and culture samples were taken for transcriptional profiling performed by RNA-Seq analysis.
Publication Title
Model-based transcriptome engineering promotes a fermentative transcriptional state in yeast.
Sample Metadata Fields
Subject
View Samples- Caenorhabditis elegans
- 26 Downloadable Samples
- Illumina HiSeq 2000
Description
Higher order chromosome structure and nuclear architecture can have profound effects on gene regulation. We analyzed how compartmentalizing the genome by tethering heterochromatic regions to the nuclear lamina affects dosage compensation in the nematode C. elegans. In this organism, the dosage compensation complex (DCC) binds both X chromosomes of hermaphrodites to repress transcription two-fold, thus balancing gene expression between XX hermaphrodites and XO males. X chromosome structure is disrupted by mutations in DCC subunits. Using X chromosome paint fluorescence microscopy, we found that X chromosome structure and subnuclear localization are also disrupted when the mechanisms that anchor heterochromatin to the nuclear lamina are defective. Strikingly, the heterochromatic left end of the X chromosome is less affected than the gene-rich middle region, which lacks heterochromatic anchors. These changes in X chromosome structure and subnuclear localization are accompanied by small, but significant levels of derepression of X-linked genes as measured by RNA-seq, without any observable defects in DCC localization and DCC-mediated changes in histone modifications. We propose a model in which heterochromatic tethers on the left arm of the X cooperate with the DCC to compact and peripherally relocate the X chromosomes, contributing to gene repression. Overall design: RNA-seq profiles of C. elegans L1 wild type hermaphrodites, cec-4, met-2 set-25, and DPY-27 RNAi. RNA-seq profiles or C. elegans. Strains are N2 Bristol strain (wild type), RB2301 cec-4(ok3124) IV, and EKM99 met-2(n4256) set-25(n5021) III. Biological replicates for each strain/stage listed separately.
Publication Title
Anchoring of Heterochromatin to the Nuclear Lamina Reinforces Dosage Compensation-Mediated Gene Repression.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
Single-cell RNA-seq (Smart-Seq2) to profile of cardiac progenitor cells Overall design: Transcriptional profiling of cultured CPCs was performed by scRNA-Seq approaches using Smart-Seq2 technology
Publication Title
In situ transcriptome characteristics are lost following culture adaptation of adult cardiac stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples