Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inter-individual variability in lymphocyte stimulation and transcriptomic response predicts mycophenolic acid sensitivity in healthy volunteers

ABSTRACT: Inter-individual variability in lymphocyte stimulation and transcriptomic response predicts mycophenolic acid sensitivity in healthy volunteers

PROVIDER: PRJNA591800 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Inter-individual variability in lymphocyte stimulation and transcriptomic response predicts mycophenolic acid sensitivity in healthy volunteers

Project description:Mycophenolic acid is an immunosuppressant commonly used to prevent renal transplant rejection and treat glomerulonephritis. Despite its widespread use, there is a clinical need to reduce solid-organ transplant rejection and improve rates of complete therapeutic response in autoimmunity. Single-cell RNA-sequencing (n=6) in lymphocytes was performed at baseline, post-stimulation, and post-mycophenolate treatment. This study identifies a polygenic transcriptomic signature in lymphocyte sub-populations predictive of mycophenolate response.

2020-07-15 | GSE141026 | GEO

Interindividual Variability in Lymphocyte Stimulation and Transcriptomic Response Predicts Mycophenolic Acid Sensitivity in Healthy Volunteers.

Project description:Mycophenolic acid (MPA) is an immunosuppressant commonly used to prevent renal transplant rejection and treat glomerulonephritis. MPA inhibits IMPDH2 within stimulated lymphocytes, reducing guanosine synthesis. Despite the widespread use of MPA, interindividual variability in response remains with rates of allograft rejection up to 15% and approximately half of individuals fail to achieve complete remission to lupus nephritis. We sought to identify contributors to interindividual variability in MPA response, hypothesizing that the HPRT1 salvage guanosine synthesis contributes to variability. MPA sensitivity was measured in 40 healthy individuals using an ex vivo lymphocyte viability assay. Measurement of candidate gene expression (n ± 40) and single-cell RNA-sequencing (n ± 6) in lymphocytes was performed at baseline, poststimulation, and post-MPA treatment. After stimulation, HPRT1 expression was 2.1-fold higher in resistant individuals compared with sensitive individuals (P ± 0.049). Knockdown of HPRT1 increased MPA sensitivity (12%; P ± 0.003), consistent with higher expression levels in resistant individuals. Sensitive individuals had higher IMPDH2 expression and 132% greater stimulation. In lymphocyte subpopulations, differentially expressed genes between sensitive and resistant individuals included KLF2 and LTB. Knockdown of KLF2 and LTB aligned with the predicted direction of effect on proliferation. In sensitive individuals, more frequent receptor-ligand interactions were observed after stimulation (P ± 0.0004), but fewer interactions remained after MPA treatment (P ± 0.0014). These data identify a polygenic transcriptomic signature in lymphocyte subpopulations predictive of MPA response. The degree of lymphocyte stimulation, HPRT1, KLF2, and LTB expression may serve as markers of MPA efficacy.

| S-EPMC7719379 | biostudies-literature

Inter-ethnic differences in lymphocyte sensitivity to glucocorticoids reflect variation in transcriptional response

Project description:Glucocorticoids (GCs) are steroid hormones widely used as pharmaceutical interventions, which act mainly by regulating gene expression levels. A large fraction of patients (~30%), especially those of African descent, show a weak response to treatment. To interrogate the contribution of variable transcriptional response to inter-ethnic differences, we measured in vitro lymphocyte GC sensitivity (LGS) and transcriptome-wide response to GCs in peripheral blood mononuclear cells (PBMCs) from African-American and European-American healthy donors. We found that transcriptional response after 8hrs treatment was significantly correlated with variation in LGS within and between populations. We found that NFKB1, a gene previously found to predict LGS within populations, was more strongly downregulated in European-Americans on average. NFKB1 could not completely explain population differences, however, and we found an additional 177 genes with population differences in the average log2 fold change (FDR<0.05), most of which also showed a weaker transcriptional response in AfricanAmericans. These results suggest that inter-ethnic differences in GC sensitivity reflect variation in transcriptional response at many genes, including regulators with large effects (e.g. NFKB1) and numerous other genes with smaller effects. Total RNA was obtained from paired aliquots of peripheral blood mononuclear cells treated with dexamethasone or vehicle (EtOH) for 8 and 24 hours.

2012-02-01 | E-GEOD-33649 | biostudies-arrayexpress

Inter-ethnic differences in lymphocyte sensitivity to glucocorticoids reflect variation in transcriptional response

2012-02-01 | GSE33649 | GEO

Global gene expression of hiPS cell derived cardiomyocytes from healthy volunteers

Project description:To investigate the relationship between inter-individual difference of drug susceptibility and global gene expression, gene expression profiles of human iPS cell-derived cardiomyocytes (hiPSC-CMs) generated from healthy volunteers were compared with each other.

2016-12-14 | GSE92391 | GEO

Inter-layer and inter-subject variability of circadian gene expression in human skin

Project description:Inter-layer and inter-subject variability of circadian gene expression in human skin

| PRJNA844020 | ENA

Measurement of inter-individual variability in gene expression in mouse neutrophils

Project description:We extracted RNA from C57BL/6 mouse neutrophils to measure inter-individual variability in gene expression. 5 of the 10 blood samples were analyzed separately, the other 5 were pooled then split into 5 technical replicates to measure technical variability. We could then measure inter-individual variability in gene expression and compare it to the amplitude of miRNA-guided repression by miR-223.

2016-09-21 | GSE59549 | GEO

Transcription profiling of human dermal microvascular endothelial, fibroblast, and glioblastoma cells treated with mycophenolic acid

Project description:The effect of Mycophenolic acid on primary isolated human dermal microvascular endothelial (HDMVEC) and fibroblast cells as well as human glioblastoma brain tumor cell line (U87).

2008-06-25 | E-TABM-315 | biostudies-arrayexpress

Investigation of inter- and intra-day variability of tear fluid regarding flow rate, protein concentration as well as protein composition

Project description:Purpose: Determination of inter- and intra-day variations in tear flow rate, tear fluid protein concentration as well as protein composition regarding their impact for future biomarker studies.Methods: Tear fluid was collected non-invasively from 18 healthy subjects performing Schirmer tests at four different time points repetitive in a period of two days. The tear flow rate with Schirmer test strips was measured. Proteins were extracted from strips and quantified using amino acid analysis. Protein composition was analyzed by data-independent (DIA) based mass spectrometry. To exclude any impairments to health, volunteers underwent a detailed neurological as well as an ophthalmological examination.Results: Whether tear fluid was collected from OS or OD did not affect the tear flow rate (p ≈ 0.63) or protein concentration (p ≈ 0.97) of individual subjects. Moreover, protein concentration was independent from the tear volume, so that a change in volume would only have an effect on total protein amount. When the examination days were compared, investigation of tear flow rate (p ≈ 0.001) and protein concentration (p ≈ 0.0003) indicated significant differences. Further mass spectrometric analysis of tear fluid revealed eleven differentially regulated proteins when comparing both examination days. Conclusion: Our findings provide evidence of inter-day variation in tear flow rate, tear proteome concentration and composition in healthy subjects, suggesting that inter-day variation need to be taken into consideration in biomarker research of tear fluid. Identified proteins were assigned to functions in the immune response, oxidative and reducing processes, as well as mannose metabolism.

2023-10-24 | PXD037811 | Pride

Widespread inter-individual gene expression variability in Arabidopsis thaliana

Project description:Widespread inter-individual gene expression variability in Arabidopsis thaliana

| PRJNA475542 | ENA