2. Academic Validation
  3. PIEZO1 Drives Trophoblast Fusion and Placental Development

PIEZO1 Drives Trophoblast Fusion and Placental Development

  • bioRxiv. 2025 Mar 26:2025.03.25.645313. doi: 10.1101/2025.03.25.645313.
Yang Zhang 1,  Ke Z Shan 1,  Pengfei Liang 1,  Augustus J Lowry 1,  Liping Feng 2,  Huanghe Yang 1 3 4
Affiliations

Affiliations

  • 1 Department of Biochemistry, Duke University School of Medicine, NC 27710, USA.
  • 2 Department of Obstetrics and Gynecology, Duke University School of Medicine, NC 27710, USA.
  • 3 Department of Medicine, Duke University School of Medicine, NC 27710, USA.
  • 4 Department of Neurobiology, Duke University School of Medicine, NC 27710, USA.
PMID: 40196526 DOI: 10.1101/2025.03.25.645313
Abstract

PIEZO1, a mechanosensor1,2 in endothelial cells, plays a critical role in fetal vascular development during embryogenesis3,4. 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 fusion5,6. These findings reveal PIEZO1 as a crucial mechanosensor in trophoblasts and highlight its indispensable role in trophoblast fusion and placental development, expanding our understanding of PIEZO1's functions beyond endothelial cells during pregnancy.

Keywords

PIEZO1; TMEM16F; cell fusion; phosphatidylserine; placenta; trophoblast differentiation.

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