Caparrós-Pérez Eva, Teruel-Montoya Raúl, López-Andreo Mª José, Llanos Mª Carmen, Rivera José, Palma-Barqueros Verónica, Blanco Jose E, Vicente Vicente, Martínez Constantino, Ferrer-Marín Francisca
Hematology and Medical Oncology Department. Centro Regional de Hemodonación, Morales Meseguer University Hospital, IMIB-Arrixaca, Murcia, Spain.
Red CIBERER (CB15/00055), Instituto Carlos III, Madrid, Spain.
PLoS One. 2017 Aug 16;12(8):e0183042. doi: 10.1371/journal.pone.0183042. eCollection 2017.
Understanding the underlying mechanisms of the well-substantiated platelet hyporeactivity in neonates is of interest given their implications for the clinical management of newborns, a population at higher bleeding risk than adults (especially sick and preterm infants), as well as for gaining insight into the regulatory mechanisms of platelet biology. Transcriptome analysis is useful in identifying mRNA signatures affecting platelet function. However, human fetal/neonatal platelet transcriptome analysis has never before been reported. We have used mRNA expression array for the first time to compare platelet transcriptome changes during development. Microarray analysis was performed in pure platelet RNA obtained from adult and cord blood, using the same platform in two independent laboratories. A high correlation was obtained between array results for both adult and neonate platelet samples. There was also good agreement between results in our adult samples and outcomes previously reported in three different studies. Gene enrichment analysis showed that immunity- and platelet function-related genes are highly expressed at both developmental stages. Remarkably, 201 genes were found to be differentially expressed throughout development. In particular, neonatal platelets contain higher levels of mRNA that are associated with protein synthesis and processing, while carrying significantly lower levels of genes involved in calcium transport/metabolism and cell signaling (including GNAZ). Overall, our results point to variations in platelet transcriptome as possibly underlining the hypo-functional phenotype of neonatal platelets and provide further support for the role of platelets in cellular immune response. Better characterization of the platelet transcriptome throughout development can contribute to elucidate how transcriptome changes impact different pathological conditions.
鉴于血小板低反应性在新生儿临床管理中的意义(新生儿是一个出血风险高于成年人的群体,尤其是患病和早产婴儿),以及对深入了解血小板生物学调节机制的作用,了解新生儿中充分证实的血小板低反应性的潜在机制具有重要意义。转录组分析有助于识别影响血小板功能的mRNA特征。然而,此前从未有过关于人类胎儿/新生儿血小板转录组分析的报道。我们首次使用mRNA表达阵列来比较发育过程中血小板转录组的变化。在两个独立实验室中,使用相同平台对从成人和脐带血中获得的纯血小板RNA进行微阵列分析。成人和新生儿血小板样本的阵列结果之间具有高度相关性。我们的成人样本结果与之前三项不同研究报告的结果也有很好的一致性。基因富集分析表明,免疫和血小板功能相关基因在两个发育阶段均高度表达。值得注意的是,发现有201个基因在整个发育过程中差异表达。特别是,新生儿血小板含有较高水平的与蛋白质合成和加工相关的mRNA,而参与钙转运/代谢和细胞信号传导(包括GNAZ)的基因水平则显著较低。总体而言,我们的结果表明血小板转录组的变化可能是新生儿血小板功能低下表型的基础,并为血小板在细胞免疫反应中的作用提供了进一步支持。更好地表征发育过程中的血小板转录组有助于阐明转录组变化如何影响不同的病理状况。