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PIEZO1 drives trophoblast fusion and placental development

Author

Listed:
  • Yang Zhang

    (Duke University School of Medicine
    Shenzhen Bay Laboratory)

  • Ke Z. Shan

    (Duke University School of Medicine)

  • Pengfei Liang

    (Duke University School of Medicine)

  • Augustus J. Lowry

    (Duke University School of Medicine)

  • Liping Feng

    (Duke University School of Medicine)

  • Huanghe Yang

    (Duke University School of Medicine
    Duke University School of Medicine
    Duke University School of Medicine)

Abstract

PIEZO1, a mechanosensor in endothelial cells, plays a critical role in fetal vascular development during embryogenesis. However, its expression and function in placental trophoblasts remain unexplored. Here, we demonstrate that PIEZO1 is expressed in placental villus trophoblasts, where it is essential for trophoblast fusion and placental development. Mice with trophoblast-specific PIEZO1 knockout exhibit embryonic lethality without obvious vascular defects. Instead, PIEZO1 deficiency disrupts the formation of the syncytiotrophoblast layer in the placenta. Mechanistically, PIEZO1-mediated calcium influx activates TMEM16F lipid scramblase, facilitating the externalization of phosphatidylserine, a key “fuse-me” signal for trophoblast fusion. These findings reveal PIEZO1 as a crucial mechanosensor in trophoblasts and highlight its essential role in regulating trophoblast fusion and placental development, expanding our understanding of PIEZO1’s functions beyond endothelial cells during pregnancy.

Suggested Citation

  • Yang Zhang & Ke Z. Shan & Pengfei Liang & Augustus J. Lowry & Liping Feng & Huanghe Yang, 2025. "PIEZO1 drives trophoblast fusion and placental development," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62254-3
    DOI: 10.1038/s41467-025-62254-3
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    References listed on IDEAS

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    1. Bertrand Coste & Bailong Xiao & Jose S. Santos & Ruhma Syeda & Jörg Grandl & Kathryn S. Spencer & Sung Eun Kim & Manuela Schmidt & Jayanti Mathur & Adrienne E. Dubin & Mauricio Montal & Ardem Patapout, 2012. "Piezo proteins are pore-forming subunits of mechanically activated channels," Nature, Nature, vol. 483(7388), pages 176-181, March.
    2. Alessia Deglincerti & Gist F. Croft & Lauren N. Pietila & Magdalena Zernicka-Goetz & Eric D. Siggia & Ali H. Brivanlou, 2016. "Self-organization of the in vitro attached human embryo," Nature, Nature, vol. 533(7602), pages 251-254, May.
    3. Trieu Le & Zhiguang Jia & Son C. Le & Yang Zhang & Jianhan Chen & Huanghe Yang, 2019. "An inner activation gate controls TMEM16F phospholipid scrambling," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
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