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| Status |
Public on Oct 30, 2017 |
| Title |
Thyroid State Regulates Gene Expression in Human Whole Blood Cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 TRα-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 TRα-expressing leukocytes. In addition, TH may regulate gene expression in platelets. Whole blood samples might potentially be used as a proxy for other TRα-expressing tissues in humans.
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| 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.
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| Contributor(s) |
Massolt ET, van den Hout-van Vroonhoven MC, Leeuwenburgh S, Peeters RP, Visser TJ, Meima ME, Visser WE |
| Citation(s) |
29069456 |
| |
| Submission date |
Aug 30, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Selmar Leeuwenburgh |
| E-mail(s) |
s.leeuwenburgh@erasmusmc.nl
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| Organization name |
Erasmus MC
|
| Department |
Internal medicine
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| Lab |
Thyroid lab
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| Street address |
Wytemaweg 80
|
| City |
Rotterdam |
| State/province |
Zuid-Holland |
| ZIP/Postal code |
3015 CN |
| Country |
Netherlands |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA401850 |
| SRA |
SRP127016 |
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