Single cell transcriptional signatures of the human placenta in term and preterm parturition

Abstract

More than 135 million births occur each year; yet, the molecular underpinnings of human parturition in gestational tissues, and in particular the placenta, are still poorly understood. The placenta is a complex heterogeneous organ including cells of both maternal and fetal origin, and insults that disrupt the maternal-fetal dialogue could result in adverse pregnancy outcomes such as preterm birth. There is limited knowledge of the cell type composition and transcriptional activity of the placenta and its compartments during physiologic and pathologic parturition. To fill this knowledge gap, we used scRNA-seq to profile the placental villous tree, basal plate, and chorioamniotic membranes of women with or without labor at term and those with preterm labor. Significant differences in cell type composition and transcriptional profiles were found among placental compartments and across study groups. For the first time, two cell types were identified: 1) lymphatic endothelial decidual cells in the chorioamniotic membranes, and 2) non-proliferative interstitial cytotrophoblasts in the placental villi. Maternal macrophages from the chorioamniotic membranes displayed the largest differences in gene expression (e.g. NFKB1) in both processes of labor; yet, specific gene expression changes were also detected in preterm labor. Importantly, several placental scRNA-seq transcriptional signatures were modulated with advancing gestation in the maternal circulation, and specific immune cell type signatures were increased with labor at term (NK-cell and activated T-cell signatures) and with preterm labor (macrophage, monocyte, and activated T-cell signatures). Herein, we provide a catalogue of cell types and transcriptional profiles in the human placenta, shedding light on the molecular underpinnings and non-invasive prediction of the physiologic and pathologic parturition.

Data availability

Protected Human subjects data deposited in dbGaP phs001886.v1.p1Data from other sources detailed in manuscript

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Roger Pique-Regi

    Center for Molecular Medicine and Genetics, Wayne State University, Detroit, United States
    For correspondence
    rpique@wayne.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1262-2275
  2. Roberto Romero

    Center for Molecular Medicine and Genetics, Wayne State University, Detroit, United States
    For correspondence
    prbchiefstaff@med.wayne.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4448-5121
  3. Adi L Tarca

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Edward D Sendler

    Center for Molecular Medicine and Genetics, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Yi Xu

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Valeria Garcia-Flores

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Yaozhu Leng

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Francesca Luca

    Center for Molecular Medicine and Genetics, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8252-9052
  9. Sonia S Hassan

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Nardhy Gomez-Lopez

    Department of Obstetrics and Gynecology, Wayne State University, Detroit, United States
    For correspondence
    ngomezlo@med.wayne.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (HHSN275201300006C)

  • Roberto Romero

Wayne State University (Perinatal Research Initiative)

  • Nardhy Gomez-Lopez

The funders had no role in study design, data collection and interpretation.

Ethics

Human subjects: The collection and use of human materials for research purposes were approved by the Institutional Review Boards of the Wayne State University School of Medicine 040302M1F. All participating women provided written informed consent prior to sample collection. Data sharing certification (dbGaP phs001886.v1.p1) is attached.

Reviewing Editor

  1. Stephen Parker, University of Michigan, United States

Publication history

  1. Received: September 19, 2019
  2. Accepted: December 12, 2019
  3. Accepted Manuscript published: December 12, 2019 (version 1)
  4. Version of Record published: January 8, 2020 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Roger Pique-Regi
  2. Roberto Romero
  3. Adi L Tarca
  4. Edward D Sendler
  5. Yi Xu
  6. Valeria Garcia-Flores
  7. Yaozhu Leng
  8. Francesca Luca
  9. Sonia S Hassan
  10. Nardhy Gomez-Lopez
(2019)
Single cell transcriptional signatures of the human placenta in term and preterm parturition
eLife 8:e52004.
https://doi.org/10.7554/eLife.52004

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