Context: Despite the well-recognized clinical features due to insufficient or excessive thyroid hormone (TH) levels in humans, it is largely unknown which genes are regulated by TH in human tissues. objective: To study the effect of TH on human gene expression profiles in whole blood, mainly consisting of TRa-expressing cells. Methods: We performed next-generation RNA sequencing on whole blood samples from 8 athyroid patients (4 females) on and after 4 weeks off levothyroxine replacement. Gene expression changes were analyzed through paired differential expression analysis and confirmed in a validation cohort. Weighted gene co-expression network analysis (WGCNA) was applied to identify thyroid state-related networks. Results: We detected 486 differentially expressed (DE) genes (fold-change above 1.5; multiple testing corrected P-value <0.05), of which 76 % were positively and 24 % were negatively regulated. Gene ontology (GO) enrichment analysis revealed that 3 biological processes were significantly overrepresented of which the process translational elongation showed the highest fold enrichment (7.3 fold, P=1.8 x 10-6). Comparative transcriptome analysis revealed significant overlap with DE-genes in muscle samples upon different thyroid state (1.7-fold enrichment; P=0.02). WGCNA analysis independently identified various gene clusters that correlated with thyroid state. Further GO-analysis suggested that thyroid state regulates platelet function. Conclusions: Changes in thyroid state regulate numerous genes in human whole blood, predominantly TRa-expressing leukocytes. In addition, TH may regulate gene expression in platelets. Whole blood samples might potentially be used as a proxy for other TRa-expressing tissues in humans. Overall design: Transcriptome profiling (RNA-Seq) of 8 thyroidectomized human whole blood samples, sequenced first in hypothyroid state and after levothyroxine supplementation sequenced in a hypothyroid (mild thyreotoxic state) state on a Illumina HiSeq 2500 system.
Thyroid State Regulates Gene Expression in Human Whole Blood.
Specimen part, Subject
View SamplesTo investigate the impact of the iNKT cells on the tumor-infiltrating leukocytes in TRAMP mouse prostate cancer.
Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression.
Age, Specimen part
View SamplesStress induces undifferentiated stem cells to differentiate in a way that looks like normal differentiation
Hyperosmolar stress induces global mRNA responses in placental trophoblast stem cells that emulate early post-implantation differentiation.
No sample metadata fields
View SamplesMicroarray analysis was performed to identify transcriptional changes that occur during mucociliary differentiation of human primary bronchial epithelial cells cultured at an air-liquid interface (ALI).
Transcriptional profiling of mucociliary differentiation in human airway epithelial cells.
No sample metadata fields
View SamplesNeuronal function critically depends on coordinated subcellular distribution of mRNAs. Disturbed mRNA processing and axonal transport has been found in spinal muscular atrophy and could be causative for dysfunction and degeneration of motoneurons. Despite the advances made in characterizing the transport mechanisms of several axonal mRNAs, an unbiased approach to identify the axonal repertoire of mRNAs in healthy and degenerating motoneurons has been lacking. Here we used compartmentalized microfluidic chambers to investigate the somatodendritic and axonal mRNA content of cultured motoneurons by microarray analysis. In axons, transcripts related to protein synthesis and energy production were enriched relative to the somatodendritic compartment. Knockdown of Smn, the protein deficient in spinal muscular atrophy, produced a large number of transcript alterations in both compartments. Transcripts related to immune functions, including MHC class I genes, and with roles in RNA splicing were upregulated in the somatodendritic compartment. On the axonal side, transcripts associated with axon growth and synaptic activity were downregulated. These alterations provide evidence that subcellular localization of transcripts with axonal functions as well as regulation of specific transcripts with nonautonomous functions is disturbed in Smn-deficient motoneurons, most likely contributing to the pathophysiology of spinal muscular atrophy.
Subcellular transcriptome alterations in a cell culture model of spinal muscular atrophy point to widespread defects in axonal growth and presynaptic differentiation.
Specimen part
View SamplesThe transcriptomic changes induced in the human liver cell line HepG2 by 100M menadione, 200M TBH or 50M H2O2 after treatment for 0.5, 1, 2, 4, 6, 8 and 24h.
Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach.
Cell line
View SamplesHigh-throughput mapping of cellular differentiation hierarchies from single-cell data promises to empower systematic interrogations of vertebrate development and disease. Here, we applied single-cell RNA sequencing to >92,000 cells from zebrafish embryos during the first day of development. Using a graph-based approach, we mapped a cell state landscape that describes axis patterning, germ layer formation, and organogenesis. We tested how clonally related cells traverse this landscape by developing a transposon-based barcoding approach (“TracerSeq”) for reconstructing single-cell lineage histories. Clonally related cells were often restricted by the state landscape, including a case in which two independent lineages converge on similar fates. Cell fates remained restricted to this landscape in chordin-deficient embryos. We provide web-based resources for further analysis of the single-cell data. Overall design: Single-cell mRNA sequencing of zebrafish embryonic cells. Samples1-7: Single cell libraries from untreated embryos (4-24 hours post-fertilization). Samples8-12: Single cell libraries from embryos injected with TracerSeq lineage cassette at the 1-cell stage. Samples13-18: Single cell libraries from embryos injected with sgRNA + Cas9 at the 1-cell stage.
Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo.
Cell line, Treatment, Subject
View SamplesPurpose: Epidemiological and intervention studies have attempted to link the health effects of a diet rich in fruits and vegetables with the consumption of polyphenols and their impact in neurodegenerative diseases. Studies have shown that polyphenols can cross the intestinal barrier and reach concentrations in the bloodstream able to exert effects in vivo. However, the effective uptake of polyphenols in the brain is still regarded with some reservations. Here we describe a combination of approaches to examine the putative transport of blackberry-digested polyphenols (BDP) across the blood-brain barrier (BBB) and ultimate evaluation of their beneficial effects.
Blood-brain barrier transport and neuroprotective potential of blackberry-digested polyphenols: an in vitro study.
Sex, Specimen part, Cell line, Race
View SamplesMicroarrays were used to evaluate the effects of azithromycin and an inflammatory stimulus (SMM) on human airway epithelium. Effects of azithromycin treatment were evaluated at 6, 24 and 48 hours. Effects of SMM were evaluated at 6 and 24 hours. In addition, pretreatment with azithromycin was used to evaluate the modulatory effects on SMM-induced inflammation. SMM=supernatant from microcorpulent material from human cystic fibrosis airways.
Azithromycin treatment alters gene expression in inflammatory, lipid metabolism, and cell cycle pathways in well-differentiated human airway epithelia.
No sample metadata fields
View SamplesA number of breast or colon specific genes predictive of the relapse status were used in comparing the outcome from matched fresh frozen and stored in RNAlater preservative.
Prognostic gene expression signatures can be measured in tissues collected in RNAlater preservative.
No sample metadata fields
View Samples