Many factors are believed to be involved in the differentiation of odontoblasts located in the dental pulp as they assist in the formation of dentin (Nakazato et al. 2024). In the current issue of the journal, Hosoya and colleagues present the results of their detailed investigation into the role of the polycomb protein Bmi1 in facilitating the differentiation of odontoblasts (Hosoya et al. 2025). They chose to study Bmi1, which is encoded by the B cell-specific Moloney murine leukemia virus integration site 1 because it is a member of the family of epigenetic regulatory factors affecting modification of histones and nuclear chromatin remodeling, as well as stem cell proliferation (Fitieh et al. 2021). To investigate whether Bmi1 is involved in the regulation of odontoblast differentiation, and by extension dentin formation and regeneration, Hosoya et al. (2025) used a developing rat model of mandibular tissue (embryonic day 15 through postnatal day 28), a tooth cavity repair model, and transfected KN-3 cultured cells (an immortalized rat dental mesenchymal cell line). Using a variety of techniques, including immunohistochemistry on tissue sections, immunofluorescence on cultured cells, western blotting, qRT-PCR, and histochemical staining (alizarin red to indicate mineralization) they obtained the following results: (1) the localization of Bmi1 in developing embryonic and postnatal teeth varied with developmental stage, though at times was present in a variety of hard tissue-forming cells including odontoblasts, ameloblasts, cementoblasts, and osteoblasts, underscoring its potential role in differentiation of stem cells and hard-tissue forming cells; (2) the amount of detectable Bmi1 immunostaining in odontoblasts diminished in intensity as dentin formation proceeded; (3) following cavity preparation in postnatal day 28 lower first molars, Bmi1 was first detected after 4 days in cells located close to newly forming matrix. One week following cavity preparation, reparative odontoblasts near newly formed dentin were positive for Bmi1; however, this staining disappeared 8 weeks after cavity preparation; and (4) overexpression of Bmi1 via transfection of DNA into KN-3 cells led to mineralization tissue formation (indicative of enhanced odontoblast-lineage differentiation), whereas knockdown of Bmi1 via siRNA technology resulted in decreased mineralization formation (indicating a blockage of odontoblast-lineage differentiation), reduced nuclear transition of signaling pathway molecules β-catenin and expression of Smad1/5/8 (suggesting that odontoblast differentiation may involve Bmi1 regulation via the Wnt and BMP signaling pathways). Overall, the results of this careful study suggest that the Bmi1 protein is expressed during dentin formation and regeneration in osteoblast-lineage cells, and that the presence of this protein enhanced the differentiation of osteoblasts, suggesting that it might be important for dentin regeneration therapy.