Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface.

Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface.
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DOI:
10.1101/gr.207597.116
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发表时间:
2017-03
期刊:
影响因子:
7
通讯作者:
Jones H
Jones H
中科院分区:
生物学1区
文献类型:
--
作者:
Pavličev M;Wagner GP;Chavan AR;Owens K;Maziarz J;Dunn-Fletcher C;Kallapur SG;Muglia L;Jones H

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有机体功能在很大程度上是由其基本组成部分(细胞)之间的相互作用决定的。在这项工作中,我们利用单细胞转录组学研究了胎儿胎盘滋养层细胞和母体子宫内膜基质细胞的细胞间相互作用。胎盘界面介导两个半同种异体个体(母亲和胎儿)之间的相互作用,因此是细胞相互作用的缩影。为了研究这些,我们通过评估跨细胞类型的受体-配体对的基因表达来推断细胞-细胞相互作用组。我们发现 G 蛋白偶联受体具有高度细胞类型特异性表达,这意味着配体-受体谱可能是细胞类型识别的可靠工具。此外,我们发现子宫蜕膜细胞代表了细胞间相互作用的枢纽,具有大量潜在的传入和传出信号。在子宫准备怀孕期间,蜕膜细胞与其前体子宫内膜基质成纤维细胞分化。我们表明,蜕膜化(即使在体外)增强了与胎儿沟通的能力,因为在蜕膜化过程中上调的大多数受体和配体在滋养层细胞中都有其对应物的表达。在传输的信号中,生长因子和免疫信号占主导地位,表明增强信号和抑制信号之间存在微妙的平衡。最后,这项研究提供了足月绒毛内和绒毛外滋养层基因表达谱的丰富资源,包括多核合体滋养层的转录组。
Organismal function is, to a great extent, determined by interactions among their fundamental building blocks, the cells. In this work, we studied the cell-cell interactome of fetal placental trophoblast cells and maternal endometrial stromal cells, using single-cell transcriptomics. The placental interface mediates the interaction between two semiallogenic individuals, the mother and the fetus, and is thus the epitome of cell interactions. To study these, we inferred the cell-cell interactome by assessing the gene expression of receptor-ligand pairs across cell types. We find a highly cell-type-specific expression of G-protein-coupled receptors, implying that ligand-receptor profiles could be a reliable tool for cell type identification. Furthermore, we find that uterine decidual cells represent a cell-cell interaction hub with a large number of potential incoming and outgoing signals. Decidual cells differentiate from their precursors, the endometrial stromal fibroblasts, during uterine preparation for pregnancy. We show that decidualization (even in vitro) enhances the ability to communicate with the fetus, as most of the receptors and ligands up-regulated during decidualization have their counterpart expressed in trophoblast cells. Among the signals transmitted, growth factors and immune signals dominate, and suggest a delicate balance of enhancing and suppressive signals. Finally, this study provides a rich resource of gene expression profiles of term intravillous and extravillous trophoblasts, including the transcriptome of the multinucleated syncytiotrophoblast.