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Mechanosensitive properties of astrocytes allow them to sense and respond to mechanical cues from the local environment. We confirmed that ONH astrocytes express the mechanosensitive ion channel Piezo1 in vivo. By manipulating Piezo1 knockdown or overexpression in vitro, we found that Piezo1 is necessary but insufficient for ONH astrocyte proliferation. Loss of Piezo1 can lead to cell cycle arrest at G0\/G1 phase, a possible mechanism involving decreased yes\u2010associated protein (YAP) nuclear localization and downregulation of YAP\u2010target cell cycle\u2010associated factors, including cyclin D1 and c\u2010Myc. Gene ontology enrichment analysis of differential expression genes from RNA\u2010seq data indicates that the absence of Piezo1 affects biological processes involving cell division. 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