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Impact of high platelet turnover on the platelet transcriptome: Results from platelet RNA-sequencing in patients with sepsis
- Source :
- PLoS ONE, PLoS ONE, Vol 17, Iss 1, p e0260222 (2022)
- Publication Year :
- 2021
-
Abstract
- Background Sepsis is associated with high platelet turnover and elevated levels of immature platelets. Changes in the platelet transcriptome and the specific impact of immature platelets on the platelet transcriptome remain unclear. Thus, this study sought to address whether and how elevated levels of immature platelets affect the platelet transcriptome in patients with sepsis. Methods Blood samples were obtained from patients with sepsis requiring vasopressor therapy (n = 8) and from a control group of patients with stable coronary artery disease and otherwise similar demographic characteristics (n = 8). Immature platelet fraction (IPF) was determined on a Sysmex XE 2100 analyser and platelet function was tested by impedance aggregometry. RNA from leukocyte-depleted platelets was used for transcriptome analysis by Next Generation Sequencing integrating the use of unique molecular identifiers. Results IPF (median [interquartile range]) was significantly elevated in sepsis patients (6.4 [5.3–8.7] % vs. 3.6 [2.6–4.6] %, p = 0.005). Platelet function testing revealed no differences in adenosine diphosphate- or thrombin receptor activating peptide-induced platelet aggregation between control and sepsis patients. Putative circular RNA transcripts were decreased in platelets from septic patients. Leukocyte contamination defined by CD45 abundance levels in RNA-sequencing was absent in both groups. Principal component analysis of transcripts showed only partial overlap of clustering with IPF levels. RNA sequencing showed up-regulation of 524 and down-regulation of 118 genes in platelets from sepsis patients compared to controls. Upregulated genes were mostly related to catabolic processes and protein translation. Comparison to published platelet transcriptomes showed a large overlap of changes observed in sepsis and COVID-19 but not with reticulated platelets from healthy donors. Conclusions Patients with sepsis appear to have a less degraded platelet transcriptome as indicated by increased levels of immature platelets and decreased levels of putative circular RNA transcripts. The present data suggests that increased protein translation is a characteristic mechanism of systemic inflammation.
- Subjects :
- Male
Viral Diseases
Platelet Aggregation
Physiology
Molecular biology
Gene Expression
Sequencing techniques
Medical Conditions
Mathematical and Statistical Techniques
Animal Cells
Medicine and Health Sciences
Principal Component Analysis
Multidisciplinary
Statistics
RNA sequencing
Genomics
Hematology
Body Fluids
Blood
Infectious Diseases
Physical Sciences
Medicine
Anatomy
Cellular Types
Transcriptome Analysis
Research Article
Blood Platelets
Platelets
Platelet Function Tests
Science
Cell Fractionation
Signs and Symptoms
Sepsis
Genetics
Humans
Statistical Methods
Blood Coagulation
Aged
Blood Cells
Base Sequence
Platelet Count
Sequence Analysis, RNA
Gene Expression Profiling
Biology and Life Sciences
Computational Biology
Covid 19
RNA, Circular
Cell Biology
Platelet Activation
Genome Analysis
Research and analysis methods
Molecular biology techniques
Multivariate Analysis
Clinical Medicine
Transcriptome
Platelet Aggregation Inhibitors
Mathematics
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 17
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- PloS one
- Accession number :
- edsair.doi.dedup.....65d86d5ce1aa10d4d7fa2db04e6fe2a6