PIEZO1-mediated calcium signaling reinforces mechanical properties of hair follicle stem cells to promote quiescence
Year: 2025
Type: article
Abstract: The mechanisms by which epithelial stem cells (SCs) sense mechanical cues within their niche and convert the information into biochemical signals to govern their function are not well understood. Here, we show that hair follicle SCs (HF-SCs) sense mechanical forces through cell adhesion and maintain quiescence in a PIEZO1-dependent mechanism. PIEZO1 interacts with E-cadherin in HF-SCs, and mechanical pulling of E-cadherin with a force of ~20 pN triggers PIEZO1-dependent, localized calcium flickers. Deletion of Piezo1 leads to reduced cumulative calcium influx and compromises quiescence. Single-cell genomic analyses identify a transcriptional network involving AP1 and NFATC1, which functions downstream of PIEZO1 and regulates the expression of extracellular matrix, cell adhesion, and actin cytoskeleton genes to reinforce the unique mechanical property of HF-SCs. These findings establish the force threshold necessary for PIEZO1 activation and reveal PIEZO1-dependent calcium influx as a key mechanism for sensing mechanical cues in the niche and regulating HF-SC activity.
Source: Science Advances
Authors: Jingjing Wang, Chaoyu Fu, Sophie Chang, Christopher Stephens, Haimin Li, Dongmei Wang, Yuheng C. Fu, Kathleen J. Green, Jie Yan, Rui Yi
Language: English
Topic: Hair Growth and Disorders
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
Awards: G3194474721, Genetic Analysis of MicroRNA Functions in Skin Stem Cells In Vivo, G4103079173, Desmoplakin Assembly and Function in Epidermis, Function of Desmoglein 1/Pemphigus Foliaceus Antigen, Modeling p63-associated human birth defects with systems developmental biology approaches, Transcriptional regulation of skin stem cells and their niche
OpenAlex ID: W4410809542