PIEZO1 drives trophoblast fusion and placental development

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...

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Main Authors: Yang Zhang, Ke Z. Shan, Pengfei Liang, Augustus J. Lowry, Liping Feng, Huanghe Yang
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62254-3
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author Yang Zhang
Ke Z. Shan
Pengfei Liang
Augustus J. Lowry
Liping Feng
Huanghe Yang
author_facet Yang Zhang
Ke Z. Shan
Pengfei Liang
Augustus J. Lowry
Liping Feng
Huanghe Yang
author_sort Yang Zhang
collection DOAJ
description 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.
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institution Kabale University
issn 2041-1723
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publishDate 2025-07-01
publisher Nature Portfolio
record_format Article
series Nature Communications
spelling doaj-art-6d5eb39dead341e388dbec256bbdb4df2025-08-20T03:46:15ZengNature PortfolioNature Communications2041-17232025-07-0116111010.1038/s41467-025-62254-3PIEZO1 drives trophoblast fusion and placental developmentYang Zhang0Ke Z. Shan1Pengfei Liang2Augustus J. Lowry3Liping Feng4Huanghe Yang5Department of Biochemistry, Duke University School of MedicineDepartment of Biochemistry, Duke University School of MedicineDepartment of Biochemistry, Duke University School of MedicineDepartment of Biochemistry, Duke University School of MedicineDepartment of Obstetrics and Gynecology, Duke University School of MedicineDepartment of Biochemistry, Duke University School of MedicineAbstract 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.https://doi.org/10.1038/s41467-025-62254-3
spellingShingle Yang Zhang
Ke Z. Shan
Pengfei Liang
Augustus J. Lowry
Liping Feng
Huanghe Yang
PIEZO1 drives trophoblast fusion and placental development
Nature Communications
title PIEZO1 drives trophoblast fusion and placental development
title_full PIEZO1 drives trophoblast fusion and placental development
title_fullStr PIEZO1 drives trophoblast fusion and placental development
title_full_unstemmed PIEZO1 drives trophoblast fusion and placental development
title_short PIEZO1 drives trophoblast fusion and placental development
title_sort piezo1 drives trophoblast fusion and placental development
url https://doi.org/10.1038/s41467-025-62254-3
work_keys_str_mv AT yangzhang piezo1drivestrophoblastfusionandplacentaldevelopment
AT kezshan piezo1drivestrophoblastfusionandplacentaldevelopment
AT pengfeiliang piezo1drivestrophoblastfusionandplacentaldevelopment
AT augustusjlowry piezo1drivestrophoblastfusionandplacentaldevelopment
AT lipingfeng piezo1drivestrophoblastfusionandplacentaldevelopment
AT huangheyang piezo1drivestrophoblastfusionandplacentaldevelopment