Systems biology evaluation of cell-free amniotic fluid transcriptome of term and preterm infants to detect fetal maturity.
Systems biology evaluation of cell-free amniotic fluid transcriptome of term and preterm infants to detect fetal maturity.
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DOI：
10.1186/s12920-015-0138-5
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发表时间：
2015-10-22
影响因子：
2.7
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Kamath-Rayne BD;Du Y;Hughes M;Wagner EA;Muglia LJ;DeFranco EA;Whitsett JA;Salomonis N;Xu Y
羊水（AF）是胎儿的近端流体，其含有比母体血清更高量的无细胞胎儿RNA/DNA，从而使其成为用于鉴定预测胎儿发育和器官成熟的新型生物标志物的有希望的来源。我们的目的是比较妊娠期不同时间点的AF转录组谱，以证明独特的遗传特征，这些遗传特征可作为指示胎儿成熟的潜在生物标志物。我们从16名妇女在不同的时间点在怀孕：4从18至24周，6从34至36周，6从39至40周的AF RNA。对无细胞RNA进行RNA测序。结合细胞类型和途径预测进行基因表达和剪接分析。使用高置信度细胞分子标记物，在妊娠不同时间点进行的样本水平分析表明，与宫内环境和胎儿呼吸、消化和胎儿外部屏障组织中发现的细胞类型有很强的相关性。虽然一些RNA和剪接变体在整个妊娠期间存在，但许多转录物在妊娠的不同时间点独特表达，并与不同的新生儿合并症（呼吸窘迫和灌胃喂养）相关，表明胎儿不成熟。AF转录组在妊娠的不同时间点表现出独特的细胞/器官选择性表达模式，可以潜在地识别胎儿器官成熟度并预测新生儿发病率。开发指示多器官系统成熟的新型生物标志物可以改善我们目前仅关注肺部的胎儿成熟度测试方法，并将更好地告知有关分娩时机的产科决策。本文的在线版本（doi：10.1186/s12920-015-0138-5）包含补充材料，可供授权用户使用。
Amniotic fluid (AF) is a proximal fluid to the fetus containing higher amounts of cell-free fetal RNA/DNA than maternal serum, thereby making it a promising source for identifying novel biomarkers that predict fetal development and organ maturation. Our aim was to compare AF transcriptomic profiles at different time points in pregnancy to demonstrate unique genetic signatures that would serve as potential biomarkers indicative of fetal maturation. We isolated AF RNA from 16 women at different time points in pregnancy: 4 from 18 to 24 weeks, 6 from 34 to 36 weeks, and 6 from 39 to 40 weeks. RNA-sequencing was performed on cell-free RNA. Gene expression and splicing analyses were performed in conjunction with cell-type and pathway predictions. Sample-level analysis at different time points in pregnancy demonstrated a strong correlation with cell types found in the intrauterine environment and fetal respiratory, digestive and external barrier tissues of the fetus, using high-confidence cellular molecular markers. While some RNAs and splice variants were present throughout pregnancy, many transcripts were uniquely expressed at different time points in pregnancy and associated with distinct neonatal co-morbidities (respiratory distress and gavage feeding), indicating fetal immaturity. The AF transcriptome exhibits unique cell/organ-selective expression patterns at different time points in pregnancy that can potentially identify fetal organ maturity and predict neonatal morbidity. Developing novel biomarkers indicative of the maturation of multiple organ systems can improve upon our current methods of fetal maturity testing which focus solely on the lung, and will better inform obstetrical decisions regarding delivery timing. The online version of this article (doi:10.1186/s12920-015-0138-5) contains supplementary material, which is available to authorized users.