<b><i>Piezo1</i></b><b> balances the osteogenic-tenogenic plasticity of periosteal progenitor cells through the YAP pathway</b>

The extremity tendons and bones are derived from limb bud mesenchyme, which eventually become cells of different tissues. Despite their common origin, it was widely believed that tenocytes and skeletal cells are distinct lineages without interconversion. However, we found that periosteal skeletal progenitor cells could transform between osteogenic and tenogenic commitment. SCX can label the periosteal progenitor cell population. Loss of<i> Piezo1</i> arrests the periosteal progenitor cells in a progenitor state. <i>Piezo1</i> deficiency leads to upregulation of<i> Scx</i> expression due to the inhibited YAP nuclear localization. Loss of <i>Piezo1</i> showed increased tenogenic marker genes and decreased osteogenic marker genes. The periosteal progenitor cells can regenerate the injured tendon more robustly when <i>Piezo1</i> is absent. Taken together, our data reveal that periosteal SCX+ progenitor cells compromise the osteogenic ability and acquire the tenocyte-biased lineage commitment after loss of<i> Piezo1</i>, providing a strategy to modulate the periosteal progenitor cells for tissue regeneration.