High-throughput mRNA-seq atlas of human placenta shows vast transcriptome remodeling from first to third trimester.
High-throughput mRNA-seq atlas of human placenta shows vast transcriptome remodeling from first to third trimester.
复制标题
人类胎盘的高通量 mRNA-seq 图谱显示从妊娠早期到晚期的巨大转录组重塑。
DOI：
10.1101/2023.06.06.543972
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
Gonzalez,TaniaL;Wertheimer,Sahar;Flowers,AmyE;Wang,Yizhou;Santiskulvong,Chintda;Clark,EkaterinaL;Jefferies,CarolineA;Lawrenson,Kate;Chan,JessicaL;Joshi,NikhilV;Zhu,Yazhen;Tseng,Hsian-Rong;Karumanchi,SAnanth;Williams,John;
胎盘由绒毛组成，在整个妊娠过程中发生巨大变化。了解持续妊娠的差异对于确定特定时间绒毛在妊娠中的作用以及开发母婴健康的生物标记物和预后指标至关重要。标准的信使核糖核酸图谱是通过对124个妊娠早期和43个妊娠晚期的人类胎盘进行下一代测序来建立的。确定了稳定表达的基因(SEG)，这些基因在三个月之间没有不同，并且具有低变异性。对调整了胎儿性别的早孕和晚孕进行了差异表达分析，然后对23个匹配的妊娠进行了子分析，以使用相同的遗传和环境背景控制受试者的变异性。胎盘表达14,979个多腺化基因，高于测序噪声(每百万 >； 转录0.66)，在整个妊娠期间有10.7%的片段。差异表达基因(Deg)占全队列基因的86.7%[假发现率 <； 0.05]。折叠变化在全队列和子分析之间高度相关(Pearson = 0.98)。在更严格的阈值下(FDR <； 0.001，Fold Change>；1.5)，仍有50.1%的DEGS(3,353个在第一个月上调，4,155个在晚期妊娠上调)。这是最大的健康人胎盘在整个妊娠期间的mRNA图谱，控制了遗传和环境因素，显示了从怀孕早期到晚期绒毛的实质性变化。特定的差异和片段可以用来了解绒毛在整个妊娠过程中的特定作用，并开发出跨越妊娠的胎盘健康的早期生物标志物，这些生物标志物可用于未来母婴健康的生物标志物的开发。
The placenta, composed of chorionic villi, changes dramatically across gestation. Understanding differences in ongoing pregnancies are essential to identify the role of chorionic villi at specific times in gestation and develop biomarkers and prognostic indicators of maternal–fetal health. The normative mRNA profile is established using next-generation sequencing of 124 first trimester and 43 third trimester human placentas from ongoing healthy pregnancies. Stably expressed genes (SEGs) not different between trimesters and with low variability are identified. Differential expression analysis of first versus third trimester adjusted for fetal sex is performed, followed by a subanalysis with 23 matched pregnancies to control for subject variability using the same genetic and environmental background. Placenta expresses 14,979 polyadenylated genes above sequencing noise (transcripts per million > 0.66), with 10.7% SEGs across gestation. Differentially expressed genes (DEGs) account for 86.7% of genes in the full cohort [false discovery rate (FDR) < 0.05]. Fold changes highly correlate between the full cohort and subanalysis (Pearson = 0.98). At stricter thresholds (FDR < 0.001, fold change > 1.5), there remains 50.1% DEGs (3353 upregulated in first and 4155 upregulated in third trimester). This is the largest mRNA atlas of healthy human placenta across gestation, controlling for genetic and environmental factors, demonstrating substantial changes from first to third trimester in chorionic villi. Specific differences and SEGs may be used to understand the specific role of the chorionic villi throughout gestation and develop first trimester biomarkers of placental health that transpire across gestation, which can be used for future development of biomarkers for maternal–fetal health.