Systemic transcriptome comparison between early- And late-onset pre-eclampsia shows distinct pathology and novel biomarkers.
Systemic transcriptome comparison between early- And late-onset pre-eclampsia shows distinct pathology and novel biomarkers.
复制标题
早期和晚发型子痫前期的系统转录组比较显示出不同的病理和新的生物标志物。
DOI：
10.1111/cpr.12968
复制
发表时间：
2021-03
影响因子：
8.5
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Guo F;Zhang B;Yang H;Fu Y;Wang Y;Huang J;Cheng M;Li X;Shen Z;Li L;He P;Xiang AP;Wang S;Zhang H
子痫前期是孕期发病和死亡的主要原因。尽管这种疾病的两种类型，即早发型子痫前期（EOPE）和晚发型子痫前期（LOPE）有所不同，但其潜在病理机制仍不明确。我们旨在揭示两者的差异，并确定EOPE和LOPE的新型生物标志物。
为研究子痫前期的病理，我们对胎盘和外周血转录组进行了全面比较。整合母胎界面的单细胞转录组学数据，以确定EOPE和LOPE的新型生物标志物，并在患者中进一步在蛋白质或mRNA水平进行验证。
我们发现，EOPE患者胎盘的转录组与相应对照组相比存在显著差异，而LOPE患者胎盘转录组则无此差异。相反，LOPE患者外周血转录组与对照组的差异比EOPE患者更为显著。重要的是，我们发现子痫前期的几种经典生物标志物在绒毛外滋养层和合体滋养层中特异性表达，且仅在EOPE中上调，这表明这些生物标志物不应一概而论地应用于所有子痫前期患者。我们还分别从胎盘和外周血的差异表达基因（DEGs）中确定了EOPE和LOPE的新型生物标志物。新的生物标志物EBI3、IGF2、ORMDL3、GATA2和KIR2DL4已通过患者血液样本进行了实验验证。
我们的数据表明EOPE和LOPE具有不同的病理特征，并揭示了可用于子痫前期诊断的新型生物标志物。
示意图展示了早发型（EOPE）和晚发型子痫前期（LOPE）之间不同的发病机制。EOPE和LOPE的差异体现在多个层面，如风险因素、信号通路以及受疾病影响/导致疾病的组织。基于EOPE和LOPE发病机制的差异，可以识别特定的生物标志物，并通过检测胎盘分泌蛋白或母体血细胞转录本来区分这两种疾病。
Pre‐eclampsia is a leading cause of morbidity and mortality during pregnancy. Although the two forms of this disorder, early‐ (EOPE) and late‐onset of pre‐eclampsia (LOPE) are different, the underlying pathology remains elusive. We aim to unravel the difference and to identify novel biomarkers for EOPE and LOPE. A complete comparison of both placental and peripheral blood transcriptomes was performed to investigate the pathology of pre‐eclampsia. Single‐cell transcriptomics of the maternal‐fetal interface were integrated to identify novel biomarkers for EOPE and LOPE which were further verified at protein or mRNA level in patients. We found that the transcriptomes of placentae from EOPE, but not LOPE, were significantly different from their respective controls. Conversely, the transcriptomes of peripheral blood from LOPE were more different from their controls than EOPE. Importantly, we identified that several classical biomarkers of pre‐eclampsia were expressed specifically in extravillous trophoblast and syncytiotrophoblast and only upregulated in EOPE, suggesting they should not be applied to all pre‐eclampsia patients in general. We further identified novel biomarkers for EOPE and LOPE from differentially expressed genes (DEGs) of placental and peripheral blood, respectively. The new biomarkers EBI3, IGF2, ORMDL3, GATA2 and KIR2DL4 were experimentally verified with patient blood samples. Our data demonstrate distinct pathology of EOPE and LOPE, and uncover new biomarkers that can be applied in diagnosis for pre‐eclampsia. The schematic diagram shows the distinct pathogenesis between early‐ (EOPE) and late‐onset pre‐eclampsia (LOPE). The difference between EOPE and LOPE is demonstrated at several layers, such as risk factors, signalling pathways and disease affected/causing tissues. Based on divergence of EOPE and LOPE pathogenesis, specific biomarkers can be identified and used to distinguish both diseases by testing placental secreted proteins or maternal blood cell transcripts.
登录
查看更多内容
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
DOI：
10.1111/j.1471-0528.2006.00882.x
发表时间：
2006-05-01
影响因子：
5.8
作者：
Egbor, M;Ansari, T;Sibbons, PD
通讯作者：
Sibbons, PD
影响因子：
8.3
作者：
Perschbacher, Katherine J.;Deng, Guorui;Grobe, Justin L.
通讯作者：
Grobe, Justin L.
DOI：
10.1007/978-1-60761-987-1_18
发表时间：
2011-01-01
期刊：
DATA MINING IN PROTEOMICS: FROM STANDARDS TO APPLICATIONS
影响因子：
--
作者：
Kohl, Michael;Wiese, Sebastian;Warscheid, Bettina
通讯作者：
Warscheid, Bettina
影响因子：
15.9
作者：
Maynard, SE;Min, JY;Karumanchi, SA
通讯作者：
Karumanchi, SA