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Cilia beating of ependymal cells regulates adult neural stem cell quiescence via mechanical forces mediated by PKD1/2-TRPM3.
Neuron, DOI: 10.1016/j.neuron.2026.04.031 (2026)
In many tissues, stem cells are found lining fluid-filled cavities, and their neighboring niche cells include cells with beating cilia. However, the role of mechanical forces created by cilia beating on stem cells remains elusive. We developed an approach to transiently inhibit the cilia beating of ependymal cells (ECs) lining the forebrain ventricle by injecting magnetic bead-coupled antibodies targeting EC cilia and then applying a magnetic field. We show that EC cilia beating enforces neural stem cell (NSC) quiescence through mechano-sensitive polycystin 1/2 (PKD1/2)- and transient receptor potential melastatin 3 (TRPM3)-mediated Ca2+ transients. Only a few hours of EC cilia beating inhibition triggered NSC activation in vivo . CRISPR-Cas9-mediated deletion of TRPM3 or PKD1/2 in NSCs phenocopied the effect of EC cilia beating inhibition, whereas pharmacological activation of TRPM3 rescued NSC quiescence in the absence of cilia beating. Our data reveal that mechanical forces generated by EC cilia beating regulate NSC quiescence/activation dynamics.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Ca2+ Signaling ; Cilia Beating ; Ependymal Cells ; Imaging ; Mechanical Forces ; Neural Stem Cells ; Nscs ; Pkd1/2 ; Subventricular Zone ; Trpm3
ISSN (print) / ISBN
0896-6273
e-ISSN
1097-4199
Journal
Neuron
Publisher
Elsevier
Publishing Place
Cambridge, Mass.
Reviewing status
Peer reviewed
Institute(s)
Institute of Stem Cell Research (ISF)