Circular RNA Sequencing of Maternal Platelets: A Novel Tool for the Identification of Pregnancy-Specific Biomarkers.

BACKGROUND: In the first trimester of pregnancy, the maternal platelet is directly involved in a positive feedback mechanism that facilitates invasion of the extravillous trophoblast into the maternal spiral arteries. Dysfunctional trophoblast invasion with defective deep placentation is primordial...

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Publicado en:Clinical Chemistry Vol. 67; no. 3; pp. 508 - 518
Autores principales: Oudejans, Cees, Manders, Vera, Visser, Allerdien, Keijser, Remco, Min, Naomi, Poutsma, Ankie, Mulders, Joyce, van den Berkmortel, Tarah, Wigman, Di-Jan, Blanken, Britt, Jongejan, Aldo, Pajkrt, Eva, de Boer, Marjon, Sistermans, Erik A., Sie, Daoud, Best, Myron G., Würdinger, Tom, Afink, Gijs
Formato: Journal Article
Publicado: Oxford University Press / USA Mar2021
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar2021
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      pub: Oxford University Press / USA
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        10.1093/clinchem/hvaa249
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        atl: Circular RNA Sequencing of Maternal Platelets: A Novel Tool for the Identification of Pregnancy-Specific Biomarkers.
      aug:
        au:
          Oudejans, Cees
          Manders, Vera
          Visser, Allerdien
          Keijser, Remco
          Min, Naomi
          Poutsma, Ankie
          Mulders, Joyce
          van den Berkmortel, Tarah
          Wigman, Di-Jan
          Blanken, Britt
          Jongejan, Aldo
          Pajkrt, Eva
          de Boer, Marjon
          Sistermans, Erik A.
          Sie, Daoud
          Best, Myron G.
          Würdinger, Tom
          Afink, Gijs
        affil: Department of Clinical Chemistry, Amsterdam UMC, VU University Medical Center, Amsterdam, the Netherlands.
      sug:
      ab: BACKGROUND: In the first trimester of pregnancy, the maternal platelet is directly involved in a positive feedback mechanism that facilitates invasion of the extravillous trophoblast into the maternal spiral arteries. Dysfunctional trophoblast invasion with defective deep placentation is primordial in the etiology of the “great obstetrical syndromes.” METHODS: In this proof-of-concept study, using transcriptome analysis of circular RNA (circRNA) following RNA sequencing of maternal platelets, we tested whether pregnancy-specific circRNA markers could be identified in the first trimester of normal pregnancies. Differential transcript expression analysis of circRNAs, as predicted by Accurate CircRNA Finder Suite, CircRNA Identifier (version 2), and Known and Novel Isoform Explorer, was done using thromboSeq.R with variation of multiple settings. Test performance was checked for (a) de novo circRNA identification using the novel platelet-specific Plt-circR4 as a positive control, (b) complete segregation of groups (pregnant vs nonpregnant) after heat map–dendrogram clustering, (c) identification of pregnancy-specific circRNA markers at a false discovery rate (FDR) <0.05, and (d) confirmation of differentially expressed circRNA markers with an FDR <0.05 by an independent method, reverse transcription–quantitative PCR. RESULTS: Of the differentially expressed circRNAs with P values <0.05, 41 circRNAs were upregulated (logFC >2), and 52 circRNAs were downregulated (logFC less than -2) in first-trimester platelet RNA. Of these, nuclear receptor-interacting protein 1 circRNA covering exons 2 and 3 of the 50-untranslated region was pregnancy specific with upregulation in first-trimester maternal platelets compared to nonpregnant controls. CONCLUSION: CircRNA sequencing of first-trimester maternal platelets permits the identification of novel pregnancy-specific RNA biomarkers. Future use could include the assessment of maternal and fetal well-being.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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