Foreign body reaction (FBR), initiated by adherence of macrophages to biomaterials, is associated with several complications.
Gene expression study of monocytes/macrophages during early foreign body reaction and identification of potential precursors of myofibroblasts.
Specimen part
View SamplesThe expression level for 15 887 transcripts in lymphoblastoid cell lines from 19 monozygotic twin pairs (10 male, 9 female) were analysed for the effects of genotype and sex. On an average, the effect of twin pairs explained 31% of the variance in normalized gene expression levels, consistent with previous broad sense heritability estimates. The effect of sex on gene expression levels was most noticeable on the X chromosome, which contained 15 of the 20 significantly differentially expressed genes. A high concordance was observed between the sex difference test statistics and surveys of genes escaping X chromosome inactivation. Notably, several autosomal genes showed significant differences in gene expression between the sexes despite much of the cellular environment differences being effectively removed in the cell lines. A publicly available gene expression data set from the CEPH families was used to validate the results. The heritability of gene expression levels as estimated from the two data sets showed a highly significant positive correlation, particularly when both estimates were close to one and thus had the smallest standard error. There was a large concordance between the genes significantly differentially expressed between the sexes in the two data sets. Analysis of the variability of probe binding intensities within a probe set indicated that results are robust to the possible presence of polymorphisms in the target sequences.
Replicated effects of sex and genotype on gene expression in human lymphoblastoid cell lines.
Sex
View SamplesThe lncRNA LOC100130476 (named as WAKMAR2) was found to be down-regulated in epidermal keratinocytes in human chronic non-healing wounds compared to normal acute wounds and the intact skin. However, its biological role in keratinocytes during wound repair has not been studied.
WAKMAR2, a Long Noncoding RNA Downregulated in Human Chronic Wounds, Modulates Keratinocyte Motility and Production of Inflammatory Chemokines.
Specimen part
View SamplesThyroid hormone is crucial for normal brain development. Thyroid hormone transporters control thyroid hormone homeostatis in brain. Mutations in the thyroid hormone transporter MCT8 result in a complex endocrine and neurological phenotype.
Transcriptional profiling of fibroblasts from patients with mutations in MCT8 and comparative analysis with the human brain transcriptome.
Specimen part
View SamplesTo understand the population genetics of structural variants (SVs), and their effects on phenotypes, we developed an approach to mapping SVs, particularly transpositions, segregating in a sequenced population, and which avoids calling SVs directly. The evidence for a potential SV at a locus is indicated by variation in the counts of short-reads that map anomalously to the locus. These SV traits are treated as quantitative traits and mapped genetically, analogously to a gene expression study. Association between an SV trait at one locus and genotypes at a distant locus indicate the origin and target of a transposition. Using ultra-low-coverage (0.3x) population sequence data from 488 recombinant inbred Arabidopsis genomes, we identified 6,502 segregating SVs. Remarkably, 25% of these were transpositions. Whilst many SVs cannot be delineated precisely, PCR validated 83% of 44 predicted transposition breakpoints. We show that specific SVs may be causative for quantitative trait loci for germination, fungal disease resistance and other phenotypes. Further we show that the phenotypic heritability attributable to sequence anomalies differs from, and in the case of time to germination and bolting, exceeds that due to standard genetic variation. Gene expression within SVs is also more likely to be silenced or dysregulated, as inferred from RNA-seq data collected from a subset of just over 200 of the MAGIC lines. This approach is generally applicable to large populations sequenced at low-coverage, and complements the prevalent strategy of SV discovery in fewer individuals sequenced at high coverage. Overall design: 209 samples consisting of different inbred lines from the Multiparent Advance Generation InterCross (MAGIC) population in the reference plant, Arabidopsis thaliana. For each sample, RNA was collected from the aerial shoot at the 4th true leaf stage, and Illumina mRNA-seq libraries were constructed (a single library was constructed with each line; that is, each MAGIC line is represented by one biological replicate). Using these libraries, which were non-stranded, paired-end 100 bp RNA-seq Illumina reads were generated for each sample, and used to quantify gene expresison in each MAGIC line. The resulting expression phenotypes are suitable for describing the impacts of genetic variation in the MAGIC line founders on the control of gene expression.
Genomic Rearrangements in <i>Arabidopsis</i> Considered as Quantitative Traits.
Subject
View SamplesContext: 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 SamplesGenome-wide expression studies were performed on dermal fibroblasts from Sotos syndrome patients with a confirmed NSD1 abnormality and compared with age-sex matched controls.
Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway.
Specimen part, Disease, Disease stage, Treatment
View SamplesComparison of the transcriptional profiles of full-thickness murine skin harboring tissue resident memory T cells exposed to specific or control trigger Overall design: Expression profiling by high throughput sequencing
T cell memory. Skin-resident memory CD8⁺ T cells trigger a state of tissue-wide pathogen alert.
No sample metadata fields
View SamplesWe studied two growth phases- proliferation, and expansion in first pair of leaves in Arabidosis using two different overexpression lines of PID gene. Ectopic expression of PID lead to small rosette and leaf phenotype. Overall design: We used first pair of leaves from proliferation ( 9 DAS-days after stratification) and expansion (16 DAS) stage from wild type Col-0 ecotype, 35S::PID10, 35S::PID21. Three genotype, three biological replicates, two time points (=18 sample). Experiment repeated twice generating two reads in two lanes i.e. L001 & L002 for each sample. Results calculated after combining reads from both lanes (=18x2=36 raw files; 2 for each sample)
Perturbation of Auxin Homeostasis and Signaling by <i>PINOID</i> Overexpression Induces Stress Responses in Arabidopsis.
Specimen part, Subject
View SamplesBackground. Cellular senescence is a mechanism that virtually irreversibly suppresses the proliferative capacity of cells in response to various stress signals. This includes the expression of activated oncogenes, which cause Oncogene-Induced Senescence (OIS). A body of evidence points to the involvement of chromatin reorganization, including the formation of senescence-associated heterochromatic foci (SAHF). The nuclear lamina (NL) is an important contributor to genome organization and has been involved in cellular senescence and organismal aging. It interacts with multiple regions of the genome called lamina-associated domains (LADs). Some LADs are cell type-specific, while others are conserved between cell types and are referred to as constitutive LADs. Here, we used DamID to investigate the changes in genome-NL interactions in a model of OIS triggered by the expression of the BRAFV600E oncogene.Results. We found that OIS cells lose most of their constitutive LADs (cLADS), suggesting the loss of a specific mechanism that targets cLADs to the NL. In addition, multiple genes relocated to the NL. Unexpectedly, they were not repressed, implying the abrogation of the repressive activity of the NL during OIS. Finally, OIS cells displayed an increased association of telomeres with the NL.Conclusions. Our study reveals that senescent cells acquire a new type of LAD organization and suggest the existence of as yet unknown mechanisms that tether cLADs to the NL and repress gene expression at the NL.
Massive reshaping of genome-nuclear lamina interactions during oncogene-induced senescence.
Specimen part, Cell line, Subject, Time
View Samples