RNA Network Interactions During Differentiation of Human Trophoblasts.
RNA Network Interactions During Differentiation of Human Trophoblasts.
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DOI：
10.3389/fcell.2021.677981
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发表时间：
2021
影响因子：
5.5
通讯作者：
Sadovsky Y
中科院分区：
文献类型：
--
作者：
Chu T;Mouillet JF;Cao Z;Barak O;Ouyang Y;Sadovsky Y
在人胎盘中，两层滋养细胞将母体血液与绒毛基底膜和胎儿毛细血管内皮细胞分开。内层在妊娠早期是完整的，后来变得不连续，由增殖的单核细胞滋养细胞组成，它们融合并分化形成外层的多核合胞滋养细胞。由于合体滋养细胞负责母胎交换的关键功能，严格调节这一分化过程对胎盘的正常发育和功能作用至关重要。人类妊娠期间滋养细胞融合和分化的分子机制尚不清楚。为了破译非编码rna （ncRNAs）在这一过程中的相互作用，我们将培养的原代人滋养细胞暴露于标准的体外分化条件或已知阻碍这一分化过程的条件下，即暴露于缺氧（O2 < 1%）或在培养基中添加二甲亚砜（DMSO, 1.5%）。利用下一代测序技术，我们分析了受缺氧和DMSO协调调节的滋养层lncRNAs、miRNAs和mrna的差异表达。此外，我们建立了构建lncRNA-miRNA-mRNA共表达网络的模型，并通过间接基因本体分析推断lncrna和mirna的功能。这项研究提高了我们对滋养细胞分化过程中ncRNAs和mrna之间相互作用的认识，并确定了常见妊娠疾病（如胎儿生长受限或先兆子痫）中可能受损的关键生物学过程。
In the human placenta, two trophoblast cell layers separate the maternal blood from the villous basement membrane and fetal capillary endothelial cells. The inner layer, which is complete early in pregnancy and later becomes discontinuous, comprises the proliferative mononuclear cytotrophoblasts, which fuse together and differentiate to form the outer layer of multinucleated syncytiotrophoblasts. Because the syncytiotrophoblasts are responsible for key maternal-fetal exchange functions, tight regulation of this differentiation process is critical for the proper development and the functional role of the placenta. The molecular mechanisms regulating the fusion and differentiation of trophoblasts during human pregnancy remain poorly understood. To decipher the interactions of non-coding RNAs (ncRNAs) in this process, we exposed cultured primary human trophoblasts to standard in vitro differentiation conditions or to conditions known to hinder this differentiation process, namely exposure to hypoxia (O2 < 1%) or to the addition of dimethyl sulfoxide (DMSO, 1.5%) to the culture medium. Using next generation sequencing technology, we analyzed the differential expression of trophoblastic lncRNAs, miRNAs, and mRNAs that are concordantly modulated by both hypoxia and DMSO. Additionally, we developed a model to construct a lncRNA-miRNA-mRNA co-expression network and inferred the functions of lncRNAs and miRNAs via indirect gene ontology analysis. This study improves our knowledge of the interactions between ncRNAs and mRNAs during trophoblast differentiation and identifies key biological processes that may be impaired in common gestational diseases, such as fetal growth restriction or preeclampsia.