A spatially organized <i>Cd24a</i>⁺/<i>Pax9</i>⁺ stem cell core governs postnatal tooth establishment.

Abstract

Mineralized tissues are fundamental in mechanical support and protection in vertebrates. Their formation by progenitor cells during development remains elusive. Here, we show that the postnatal establishment of the molar teeth was governed by a spatially organized core of <i>Cd24a</i>⁺/<i>Pax9</i>⁺ progenitors that persisted into adulthood. <i>Cd24a</i>⁺ cells gave rise to the dentin-pulp complex, while <i>Pax9</i>⁺ ones mainly generated periodontal tissues. During development, guided by alveolar bone-derived PDGFB (platelet-derived growth factor, B polypeptide), <i>Cd24a</i>⁺/<i>Pax9</i>⁺ cells gradually concentrated on the apical region during the crown-to-root transition, collectively migrated and formed dental root. Cell ablation and conditional Wnt knockout notably compromised tooth establishment. Single-cell RNA sequencing, CUT&Tag, and spatial mapping further revealed distinct features of <i>Cd24a</i>⁺/<i>Pax9</i>⁺ cells and their cellular organization. Last, the <i>CD24</i>⁺/<i>PAX9</i>⁺ core was also present in human teeth, suggesting it as a conserved developmental program. Together, our work underscores the role of spatially organized dental stem cells in the postnatal establishment of a model mineralized organ in mammals.