Patterns of Maternal Neutrophil Gene Expression at 30 Weeks of Gestation, but Not DNA Methylation, Distinguish Mild from Severe Preeclampsia
| العنوان: | Patterns of Maternal Neutrophil Gene Expression at 30 Weeks of Gestation, but Not DNA Methylation, Distinguish Mild from Severe Preeclampsia |
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| المؤلفون: | Scott W. Walsh, Kellie J. Archer, Jerome F. Strauss, Marwah Al Dulaimi |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 12876, p 12876 (2021) International Journal of Molecular Sciences; Volume 22; Issue 23; Pages: 12876 |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, QH301-705.5, Neutrophils, Pregnancy Trimester, Third, Gene Expression, Biology, Catalysis, DNA sequencing, Article, Neutrophil Activation, Preeclampsia, Dioxygenases, Inorganic Chemistry, Andrology, Transcriptome, preeclampsia, chemistry.chemical_compound, Young Adult, pregnancy, neutrophils, gene expression, DNA methylation, epigenetics, protease-activated receptor 1, Pre-Eclampsia, Pregnancy, Gene expression, medicine, Humans, Epigenetics, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, Gene, QD1-999, Spectroscopy, Gene Expression Profiling, Organic Chemistry, General Medicine, medicine.disease, Computer Science Applications, DNA-Binding Proteins, Chemistry, chemistry, Case-Control Studies, Female, DNA |
| الوصف: | Neutrophils are activated and extensively infiltrate blood vessels in preeclamptic women. To identify genes that contribute to neutrophil activation and infiltration, we analyzed the transcriptomes of circulating neutrophils from normal pregnant and preeclamptic women. Neutrophils were collected at 30 weeks’ gestation and RNA and DNA were isolated for RNA sequencing and 5-hydroxy-methylcytosine (5-hmC) sequencing as an index of dynamic changes in neutrophil DNA methylation. Women with normal pregnancy who went on to develop mild preeclampsia at term had the most uniquely expressed genes (697) with 325 gene ontology pathways upregulated, many related to neutrophil activation and function. Women with severe preeclampsia who delivered prematurely had few pathways up- or downregulated. Cluster analysis revealed that gene expression in women with severe preeclampsia was an inverse mirror image of gene expression in normal pregnancy, while gene expression in women who developed mild preeclampsia was remarkably different from both. DNA methylation marks, key regulators of gene expression, are removed by the action of ten-eleven translocation (TET) enzymes, which oxidize 5-methylcytosines (5mCs), resulting in locus-specific reversal of DNA methylation. DNA sequencing for 5-hmC revealed no differences among the three groups. Genome-wide DNA methylation revealed extremely low levels in circulating neutrophils suggesting they are de-methylated. Collectively, these data demonstrate that neutrophil gene expression profiles can distinguish different preeclampsia phenotypes, and in the case of mild preeclampsia, alterations in gene expression occur well before clinical symptoms emerge. These findings serve as a foundation for further evaluation of neutrophil transcriptomes as biomarkers of preeclampsia phenotypes. Changes in DNA methylation in circulating neutrophils do not appear to mediate differential patterns of gene expression in either mild or severe preeclampsia. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88acef7787399a409afc15fc3309f26fTest http://europepmc.org/articles/PMC8657979Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....88acef7787399a409afc15fc3309f26f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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