Abstract: Objectives: Schneiderian membrane-derived mesenchymal stem cells (SMMSCs) have been reported to be osteogenic progenitor cells in vitro. However, there is controversy regarding the intrinsic osteogenic capacity of the Schneiderian membrane, and the bone formation potential of SMMSCs in vivo has never been reported. Therefore, in this study we aimed to evaluate the contribution of the Schneiderian membrane to sinus floor elevation and to verify the function of SMMSCs in cranial bone defects. Materials and methods: Bilateral sinus floor elevation with chloromethyl-benzamidodialkylcarbocyanine (CM-DiI) labeling was performed in rabbits to assess Schneiderian membrane osteogenesis. Single-cell RNA sequencing was used to characterize human Schneiderian membrane cellular subsets. SMMSCs and bone marrow-derived mesenchymal stem cells (BMSCs) were transplanted into rabbit cranial defects with Gelatin Methacryloy (GelMA) scaffolds and analyzed via micro-CT and histology. Results: Spontaneous bone formation adjacent to the Schneiderian membrane was observed. Single-cell analysis identified paired related homeobox1 (PRRX1) progenitor clusters driving endo-sinus osteogenesis. SMMSCs exhibited superior earlier bone regeneration (4 weeks) compared with BMSCs, with higher tissue volume and bone volume/total volume (BV / TV) ratios. Conclusions: The Schneiderian membrane likely contributes to osteogenesis via PRRX1⁺ progenitor lineages. SMMSCs promote accelerated early bone regeneration in cranial defects. This study provides the first in vivo validation of the osteogenic capacity of SMMSCs and defines their molecular identity at single-cell resolution.