SOX transcription factors play key roles in cell differentiation and cell fate determination during development. Using single-cell RNA-sequencing data, we examined the expression profiles of Sox genes in the mouse incisor dental pulp. Our analysis showed that Sox4, Sox5, Sox9, Sox11, and Sox12 are mainly expressed in mesenchymal stem/stromal cells (MSCs) representing osteogenic cells at different stages of differentiation. We found that in several MSCs, Sox genes co-expressed with regulatory genes such as Sp7, Satb2, Msx1, Snai2, Dlx1, Twist2, and Tfap2a. In addition, Sox family genes colocalized with Runx2 and Lef1, which are highly enriched in MSCs undergoing osteoblast differentiation. A protein interaction network analysis uncovered that CREBBP, CEBPB, TLE1, TWIST1, and members of the HDAC and SMAD families are interacting partners of RUNX2 and LEF1 during skeletal development. Collectively, the distinct expression patterns of the SOX transcription factors suggest that they play essential regulatory roles in directing lineage-specific gene expression during differentiation of MSCs.