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OBJECTIVES We set out to reprogram adult somatic oral epithelial keratinocytes into pluripotent cells for regenerative dentistry. SETTING AND SAMPLE POPULATION Immortalized murine oral keratinocyte cell (IMOK) line raised from adult mouse mucosa were cultured in vitro in our studies. MATERIALS AND METHODS Adult murine oral epithelial keratinocytes were chronically treated with TGF-β1 in vitro, and the expression of Oct4, Nanog, Sox2 and Nestin, as well as specific homeobox Gata and Pax gene family members were investigated. RESULTS We documented the induction of stem factors linked with pluripotency and/or the maintenance and regulation of stem-cell self-renewal in oral epithelial keratinocytes by TGFβ1. Moreover, we discovered that this TGF-β1-induced increase in Oct4, Nanog, Sox2 and Nestin was inhibited by SB431542, suggesting that TGF-β1 signals via the TGF-βRI receptor to induce pluripotency and stemness. CONCLUSIONS Adult oral epithelial keratinocytes treated chronically with TGF-β1 acquired phenotypic characteristics consistent with pluripotent stem cells, highlighting the facileness of reprogramming adult oral keratinocytes into an unlimited supply of pluripotent stem cells.