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

Mihaela Pavličev, Günter P Wagner, Arun Rajendra Chavan, Kathryn Owens, Jamie Maziarz, Caitlin Dunn-Fletcher, Suhas G Kallapur, Louis Muglia, Helen Jones
Author Information
  1. Mihaela Pavličev: Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
  2. Günter P Wagner: Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06511, USA.
  3. Arun Rajendra Chavan: Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06511, USA.
  4. Kathryn Owens: Center for Fetal Cellular and Molecular Therapy, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
  5. Jamie Maziarz: Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06511, USA.
  6. Caitlin Dunn-Fletcher: Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
  7. Suhas G Kallapur: Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
  8. Louis Muglia: Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
  9. Helen Jones: Center for Fetal Cellular and Molecular Therapy, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.

Abstract

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.

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Grants

  1. R00 HD068504/NICHD NIH HHS

MeSH Term

Cell Communication
Cell Line
Cells, Cultured
Decidua
Female
Humans
Maternal-Fetal Exchange
Pregnancy
Receptors, G-Protein-Coupled
Signal Transduction
Single-Cell Analysis
Transcriptome
Up-Regulation

Chemicals

Receptors, G-Protein-Coupled