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Single-cell RNA sequencing reveals placental response under environmental stress

Author

Listed:
  • Eric Buren

    (Harvard T.H. Chan School of Public Health)

  • David Azzara

    (University of Rochester)

  • Javier Rangel-Moreno

    (University of Rochester)

  • Maria de la Luz Garcia-Hernandez

    (University of Rochester)

  • Shawn P. Murphy

    (University of Rochester)

  • Ethan D. Cohen

    (University of Rochester)

  • Ethan Lewis

    (University of Rochester)

  • Xihong Lin

    (Harvard T.H. Chan School of Public Health
    Harvard University)

  • Hae-Ryung Park

    (University of Rochester)

Abstract

The placenta is crucial for fetal development, yet the impact of environmental stressors such as arsenic exposure remains poorly understood. We apply single-cell RNA sequencing to analyze the response of the mouse placenta to arsenic, revealing cell-type-specific gene expression, function, and pathological changes. Notably, the Prap1 gene, which encodes proline-rich acidic protein 1 (PRAP1), is significantly upregulated in 26 placental cell types including various trophoblast cells. Our study shows a female-biased increase in PRAP1 in response to arsenic and localizes it in the placenta. In vitro and ex vivo experiments confirm PRAP1 upregulation following arsenic treatment and demonstrate that recombinant PRAP1 protein reduces arsenic-induced cytotoxicity and downregulates cell cycle pathways in human trophoblast cells. Moreover, PRAP1 knockdown differentially affects cell cycle processes, proliferation, and cell death depending on the presence of arsenic. Our findings provide insights into the placental response to environmental stress, offering potential preventative and therapeutic approaches for environment-related adverse outcomes in mothers and children.

Suggested Citation

  • Eric Buren & David Azzara & Javier Rangel-Moreno & Maria de la Luz Garcia-Hernandez & Shawn P. Murphy & Ethan D. Cohen & Ethan Lewis & Xihong Lin & Hae-Ryung Park, 2024. "Single-cell RNA sequencing reveals placental response under environmental stress," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50914-9
    DOI: 10.1038/s41467-024-50914-9
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    References listed on IDEAS

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    1. Takeshi Hori & Hiroaki Okae & Shun Shibata & Norio Kobayashi & Eri H. Kobayashi & Akira Oike & Asato Sekiya & Takahiro Arima & Hirokazu Kaji, 2024. "Trophoblast stem cell-based organoid models of the human placental barrier," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Steve Perrin, 2014. "Preclinical research: Make mouse studies work," Nature, Nature, vol. 507(7493), pages 423-425, March.
    3. Roser Vento-Tormo & Mirjana Efremova & Rachel A. Botting & Margherita Y. Turco & Miquel Vento-Tormo & Kerstin B. Meyer & Jong-Eun Park & Emily Stephenson & Krzysztof Polański & Angela Goncalves & Lucy, 2018. "Single-cell reconstruction of the early maternal–fetal interface in humans," Nature, Nature, vol. 563(7731), pages 347-353, November.
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