Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface.
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.
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.
Mihaela
M
Pavličev
Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06511, USA.|Yale Systems Biology Institute, Yale University, West Haven, Connecticut 06516, USA.|Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Medical School, Yale University, New Haven, Connecticut 06510, USA.|Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan 48201, USA.
Günter P
GP
Wagner
Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06511, USA.
Arun Rajendra
AR
Chavan
Center for Fetal Cellular and Molecular Therapy, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Kathryn
K
Owens
Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06511, USA.
Jamie
J
Maziarz
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Caitlin
C
Dunn-Fletcher
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.
Suhas G
SG
Kallapur
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.
Louis
L
Muglia
Center for Fetal Cellular and Molecular Therapy, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.|Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.
Helen
H
Jones
D002450:Cell Communication; D002460:Cell Line; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059010:Single-Cell Analysis; D059467:Transcriptome; D015854:Up-Regulation
D043562:Receptors, G-Protein-Coupled