Whole-transcriptome sequencing uncovers core regulatory modules and gene signatures of human fetal growth restriction
Whole-transcriptome sequencing uncovers core regulatory modules and gene signatures of human fetal growth restriction
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全转录组测序揭示了人类胎儿生长受限的核心调控模块和基因特征
DOI：
10.1186/s40169-020-0259-0
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发表时间：
2020-01-28
影响因子：
10.6
通讯作者：
Kang, Jiuhong
中科院分区：
文献类型：
--
作者：
Wang, Guiying;Yu, Jun;Kang, Jiuhong
研究背景胎儿生长受限（FGR）是围产儿死亡和发病的主要原因，并对远期健康产生影响。为了确定核心基因表达网络和基因特征，结合超声确认将更有效地区分体质正常的小于胎龄儿和病理性FGR组，我们在脐带血的病例对照研究中对蛋白质编码基因、lncRNA和小RNA进行了RNA测序。结果对5对FGR病例和对照脐带血样本进行RNA测序和加权基因共表达网络分析（WGCNA）。结果显示，339个mRNA、295个lncRNA和13个miRNAs在FGR病例和对照组之间存在显著差异表达。生物信息学分析表明，这些差异表达的分子主要涉及代谢、神经、心脏和免疫系统，并鉴定出18个FGR的WGCNA模块。进一步的定量验证使用脐带血和母亲外周血从12对FGR病例和对照。Logistic回归分析和受试者工作特征曲线显示，脐带血中RP11_552M6.1、LINC 01291和Asgr 1与FGR的发生有潜在相关性，而母血中Sfrp 2、miR-432- 5 p和miR-1306- 3 p与FGR的发生有潜在相关性。结论本研究全面分析了人脐带血FGR的全转录组图谱，构建了FGR的WGCNA核心模块，并筛选出FGR的关键基因特征。这些发现为宫内扰动和FGR的候选特征提供了关键的见解。
Background Fetal growth restriction (FGR) contributes the primary cause of perinatal mortality and morbidity with impacts on the long-term health. To determine the core gene expression network and gene signatures, which in combination with ultrasound confirmation will more effectively differentiate constitutionally normal small for gestational age and pathological FGR groups, we performed RNA sequencing for protein-coding genes, lncRNAs, and small RNAs in a case-control study of umbilical cord blood. Results Five pairs of FGR case and control umbilical cord blood samples were used for RNA sequencing and weighted gene co-expression network analysis (WGCNA). Results showed that 339 mRNAs, 295 lncRNAs, and 13 miRNAs were significantly differentially expressed between FGR cases and controls. Bioinformatics analysis indicated that these differentially expressed molecules were mainly involved in metabolism, neural, cardiac, and immune systems, and identified 18 WGCNA modules for FGR. Further quantitative verification was performed using umbilical cord blood and maternal peripheral blood from 12 pairs of FGR cases and controls. The logistic regression and receiver operating characteristic curve indicated that RP11_552M6.1, LINC01291, and Asgr1 in umbilical cord blood, while Sfrp2, miR-432-5p, and miR-1306-3p in maternal peripheral blood had potential significance for FGR. Conclusions We comprehensively profiled the whole-transcriptome landscape of human umbilical cord blood with FGR, constructed the core WGCNA modules, and delineated the critical gene signatures of FGR. These findings provide key insight into intrauterine perturbations and candidate signatures for FGR.