Cilia beating of ependymal cells regulates adult neural stem cell quiescence via mechanical forces mediated by PKD1/2-TRPM3

In many tissues stem cells are located lining a fluid-filled volume 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 (EC) lining the forebrain ventricle by injecting magnetic beads-coupled antibodies targeting EC cilia and then applying a magnetic field. We show that EC cilia beating enforces neural stem cells (NSCs) quiescence through mechano-sensitive PKD1/2- and 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, while TRPM3 pharmacological activation rescued NSC quiescence in the absence of cilia beating. Our data reveal a novel regulator of stem cells exposed to fluids via the mechanical forces mediated by cilia beating.