Wnt-dependent ontogeny of acellular cementum-forming cementoblasts on the tooth root surface

The coronal acellular cementum (AC) is indispensable for periodontal attachment and represents a key target for periodontal regenerative therapies. However, the developmental origin and molecular identity of AC-forming cementoblasts remain poorly understood.

Here, through an integrated spatial and single-cell transcriptomic analysis, we identify AC-forming cementoblasts as a distinct population of noncanonical mineralizing cells enriched for cell-matrix organization and Wnt signaling signatures, distinguishing them from cellular cementum-forming cementoblasts localized in the apical portion. Lineage tracing using a Wnt inhibitory factor 1 (Wif1-creER) demonstrates that AC-forming cementoblasts originate exclusively from peri-epithelial apical Wif1+ cells of the elongating tooth root via canonical Wnt signaling activation.