The Transcriptional Signature of Growth in Human Fetal Aortic Valve Development.
The Transcriptional Signature of Growth in Human Fetal Aortic Valve Development.
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人类胎儿主动脉瓣发育生长的转录特征。
DOI：
10.1016/j.athoracsur.2018.06.034
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Seidman,ChristineE
中科院分区：
文献类型：
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作者：
GottliebSen,Danielle;Halu,Arda;Razzaque,Abdur;Gorham,JoshuaM;Hartnett,Jessica;Seidman,JonathanG;Aikawa,Elena;Seidman,ChristineE
背景在人类胎儿发育的中期，胎儿的尺寸增加十倍，同时心脏瓣膜生长并保持其功能。正常生长的人主动脉瓣的转录模式尚不清楚。方法从妊娠中期收集废弃的人主动脉瓣样本，其中6个来自妊娠早期（14、15、17周），6个来自妊娠晚期（20、21、22周）。 RNA 测序数据的网络分析确定了转录本显着增加和减少的子网络。随后的聚类分析确定了整个时间过程中的转录模式。通路富集分析确定了每个时间间隔的主要生物过程。结果我们观察到随时间进程的阶段性转录，包括细胞增殖和发育基因的早期减少（14 至 15 周）。模式规范、剪切应力和适应性免疫基因很早就被诱导。细胞粘附基因从14周增加到20周。涉及细胞分化和凋亡的阶段（17至20周）之后是内皮间质转化基因的下调，然后细胞外基质组织和稳定性增加（20至22周）。结论我们提出了一个独特的数据集，全面描述了瓣膜原基形成后的人类瓣膜发育特征，重点关注正常主动脉瓣经历显着生长所表现出的关键过程。我们建立了妊娠中期胎儿瓣膜生长的基因和过程的时间过程，并观察基因簇随时间的顺序调节。关键瓣膜生长基因是先天性心脏病治疗干预的潜在靶标，并对再生医学和组织工程具有影响。
BackgroundIn the second trimester of human fetal development, a tenfold increase in fetal size occurs while cardiac valves grow and retain their function. Patterns of transcription in normally growing human aortic valves are unknown.MethodsDiscarded human aortic valve samples were collected from the second trimester, 6 from early (14, 15, 17 weeks) and 6 from late (20, 21, 22 weeks) gestation. Network analysis of RNA sequencing data identified subnetworks of significantly increasing and decreasing transcripts. Subsequent cluster analysis identified patterns of transcription through the time course. Pathway enrichment analysis determined the predominant biological processes at each interval.ResultsWe observed phasic transcription over the time course, including an early decrease in cell proliferation and developmental genes (14 to 15 weeks). Pattern specification, shear stress, and adaptive immune genes were induced early. Cell adhesion genes were increased from 14 to 20 weeks. A phase involving cell differentiation and apoptosis (17 to 20 weeks) was followed by downregulation of endothelial-to-mesenchymal transformation genes and then by increased extracellular matrix organization and stabilization (20 to 22 weeks).ConclusionsWe present a unique data set, comprehensively characterizing human valve development after valve primordia are formed, focusing on key processes displayed by normal aortic valves undergoing significant growth. We build a time course of genes and processes in second trimester fetal valve growth and observe the sequential regulation of gene clusters over time. Critical valve growth genes are potential targets for therapeutic intervention in congenital heart disease and have implications for regenerative medicine and tissue engineering.