1. Stem Cells and Regenerative Medicine
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Derivation of trophoblast stem cells from naïve human pluripotent stem cells

  1. Chen Dong
  2. Mariana Beltcheva
  3. Paul Gontarz
  4. Bo Zhang
  5. Pooja Popli
  6. Laura A Fischer
  7. Shafqat A Khan
  8. Kyoung-mi Park
  9. Eun-Ja Yoon
  10. Xiaoyun Xing
  11. Ramakrishna Kommagani
  12. Ting Wang
  13. Lilianna Solnica-Krezel
  14. Thorold W Theunissen  Is a corresponding author
  1. Washington University School of Medicine, United States
Research Article
  • Cited 48
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Cite this article as: eLife 2020;9:e52504 doi: 10.7554/eLife.52504

Abstract

Naïve human pluripotent stem cells (hPSCs) provide a unique experimental platform of cell fate decisions during pre-implantation development, but their lineage potential remains incompletely characterized. As naïve hPSCs share transcriptional and epigenomic signatures with trophoblast cells, it has been proposed that the naïve state may have enhanced predisposition for differentiation along this extraembryonic lineage. Here we examined the trophoblast potential of isogenic naïve and primed hPSCs. We found that naïve hPSCs can directly give rise to human trophoblast stem cells (hTSCs) and undergo further differentiation into both extravillous and syncytiotrophoblast. In contrast, primed hPSCs do not support hTSC derivation, but give rise to non-self-renewing cytotrophoblasts in response to BMP4. Global transcriptome and chromatin accessibility analyses indicate that hTSCs derived from naïve hPSCs are similar to blastocyst-derived hTSCs and acquire features of post-implantation trophectoderm. The derivation of hTSCs from naïve hPSCs will enable elucidation of early mechanisms that govern normal human trophoblast development and associated pathologies.

Data availability

The accession number for the RNA-seq and ATAC-seq data is GSE138762.

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

Article and author information

Author details

  1. Chen Dong

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  2. Mariana Beltcheva

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  3. Paul Gontarz

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  4. Bo Zhang

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  5. Pooja Popli

    Department of Obstetrics and Gynecology, Center for Reproductive Health Sciences, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  6. Laura A Fischer

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  7. Shafqat A Khan

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  8. Kyoung-mi Park

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  9. Eun-Ja Yoon

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  10. Xiaoyun Xing

    Department of Genetics, Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  11. Ramakrishna Kommagani

    Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0403-0971

  12. Ting Wang

    Department of Genetics, Washington University School of Medicine, St Louis, United States
    Competing interests
    No competing interests declared.

  13. Lilianna Solnica-Krezel

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    Competing interests
    Lilianna Solnica-Krezel, Reviewing editor, eLife.

  14. Thorold W Theunissen

    Department of Developmental Biology, Washington University School of Medicine, St Louis, United States
    For correspondence
    t.theunissen@wustl.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6943-7858

Funding

Children's Discovery Institute (CDI-LI-2019-819)

  • Lilianna Solnica-Krezel
  • Thorold W Theunissen

McDonnell Center for Cellular and Molecular Neurobiology (22-3930-26275D)

  • Thorold W Theunissen

NIH Director's New Innovator Award (DP2 GM137418)

  • Thorold W Theunissen

Shipley Foundation Program for Innovation in Stem Cell Science

  • Thorold W Theunissen

Edward Mallinckrodt Jr Foundation

  • Thorold W Theunissen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Marianne E Bronner, California Institute of Technology, United States

Publication history

  1. Received: October 6, 2019
  2. Accepted: February 11, 2020
  3. Accepted Manuscript published: February 12, 2020 (version 1)
  4. Version of Record published: March 9, 2020 (version 2)

Copyright

© 2020, Dong et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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