Comparative transcriptomic analysis of human placentae at term and preterm delivery.
Comparative transcriptomic analysis of human placentae at term and preterm delivery.
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DOI：
10.1093/biolre/iox163
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发表时间：
2018-01-01
影响因子：
3.6
通讯作者：
Muglia LJ
中科院分区：
文献类型：
--
作者：
Paquette AG;Brockway HM;Price ND;Muglia LJ
在美国，每10个婴儿中就有一个早产，导致大量新生儿发病率和死亡率。目前，预防早产的预测标记物和治疗选择很少。一个健康、功能正常的胎盘对于积极的妊娠结局是必不可少的。先前的研究表明，胎盘病理可能在早产病因中发挥作用。因此，我们测试了这样的假设，即早产胎盘可能表现出独特的转录特征，与反映其异常生物学的足月样本相比，导致了这一不利结果。我们汇总了公开可用的胎盘绒毛微阵列数据以生成早产和足月样本数据集(n=6133，55个早产胎盘和78个正常足月胎盘)。我们使用微阵列线性回归(LIMMA)程序包识别差异表达的基因，并使用差分等级保守(DIRAC)识别已知生物网络中的扰动。我们鉴定了129个在足月胎盘和早产胎盘中显著差异表达的基因，其中96个基因上调，33个基因下调(P<0.05)。Dirac实验发现，与肿瘤蛋白53和磷脂酰肌醇信号转导相关的分子网络中的基因表达发生了显著变化。我们汇总了一个统一标准化的转录数据集，并确定了与胎盘发育调节和潜在的早产病理相关的新的和已建立的基因和途径。这些分析提供了一个社区资源，可以与其他高维数据集整合，以获得对正常胎盘发育及其破坏的更多洞察。与足月胎盘相比，自发早产胎盘的不同转录图谱确定了妊娠调节或潜在的致病机制。
Preterm birth affects 1 out of every 10 infants in the United States, resulting in substantial neonatal morbidity and mortality. Currently, there are few predictive markers and few treatment options to prevent preterm birth. A healthy, functioning placenta is essential to positive pregnancy outcomes. Previous studies have suggested that placental pathology may play a role in preterm birth etiology. Therefore, we tested the hypothesis that preterm placentae may exhibit unique transcriptomic signatures compared to term samples reflective of their abnormal biology leading to this adverse outcome. We aggregated publicly available placental villous microarray data to generate a preterm and term sample dataset (n = 133, 55 preterm placentae and 78 normal term placentae). We identified differentially expressed genes using the linear regression for microarray (LIMMA) package and identified perturbations in known biological networks using Differential Rank Conservation (DIRAC). We identified 129 significantly differentially expressed genes between term and preterm placenta with 96 genes upregulated and 33 genes downregulated (P-value <0.05). Significant changes in gene expression in molecular networks related to Tumor Protein 53 and phosphatidylinositol signaling were identified using DIRAC. We have aggregated a uniformly normalized transcriptomic dataset and have identified novel and established genes and pathways associated with developmental regulation of the placenta and potential preterm birth pathology. These analyses provide a community resource to integrate with other high-dimensional datasets for additional insights in normal placental development and its disruption. Distinct transcriptional profiles of spontaneous preterm birth placentae compared to term placentae identify gestational regulation or potential pathogenic mechanisms.
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DOI：
10.1111/micc.12093
发表时间：
2014-01
期刊：
Microcirculation (New York, N.Y. : 1994)
影响因子：
--
作者：
Chen DB;Zheng J
通讯作者：
Zheng J
影响因子：
4
作者：
Andraweera, Prabha H.;Dekker, Gustaaf A.;Roberts, Claire T.
通讯作者：
Roberts, Claire T.
影响因子：
15.9
作者：
Hirota, Yasushi;Daikoku, Takiko;Dey, Sudhansu K.
通讯作者：
Dey, Sudhansu K.
影响因子：
3.1
作者：
Gracie, Sara;Pennell, Craig;Gravett, Michael
通讯作者：
Gravett, Michael
影响因子：
4.3
作者：
Eddy JA;Hood L;Price ND;Geman D
通讯作者：
Geman D