Pavličev Mihaela, Wagner Günter P, Chavan Arun Rajendra, Owens Kathryn, Maziarz Jamie, Dunn-Fletcher Caitlin, Kallapur Suhas G, Muglia Louis, Jones Helen
Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Genome Res. 2017 Mar;27(3):349-361. doi: 10.1101/gr.207597.116. Epub 2017 Feb 7.
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.
机体功能在很大程度上由其基本组成部分——细胞之间的相互作用所决定。在这项研究中，我们使用单细胞转录组学方法研究了胎儿胎盘滋养层细胞与母体子宫内膜基质细胞之间的细胞-细胞相互作用组。胎盘界面介导了母亲和胎儿这两个半同种异体个体之间的相互作用，因此是细胞相互作用的典型代表。为了研究这些相互作用，我们通过评估不同细胞类型中受体-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的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鉴定的可靠工具。此外，我们发现子宫蜕膜细胞代表了一个细胞-细胞相互作用枢纽，具有大量潜在的传入和传出信号。蜕膜细胞在子宫为妊娠做准备的过程中从其前体子宫内膜基质成纤维细胞分化而来。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相应的表达。在传递的信号中，生长因子和免疫信号占主导地位，并表明增强和抑制信号之间存在微妙的平衡。最后，这项研究提供了丰富的足月绒毛内和绒毛外滋养层细胞基因表达谱资源，包括多核合体滋养层细胞的转录组。
