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The present study investigated the influence of inorganic phosphate (P<jats:sub>i<\/jats:sub>) on regulating stem cells isolated from human exfoliated deciduous teeth (SHED). SHEDs were treated with P<jats:sub>i<\/jats:sub>. Cell cycle progression and apoptosis were examined using flow cytometry analysis. Osteo\/odontogenic and adipogenic differentiation were analyzed using alizarin red S and oil red O staining, respectively. The mRNA expression profile was investigated using a high-throughput RNA sequencing technique. P<jats:sub>i<\/jats:sub> increased the late apoptotic cell population while cell cycle progression was not altered. P<jats:sub>i<\/jats:sub> upregulated osteo\/odontoblastic gene expression and enhanced calcium deposition. P<jats:sub>i<\/jats:sub>-induced mineralization was reversed by pretreatment of cells with Foscarnet, or p38 inhibitor. P<jats:sub>i<\/jats:sub> treatment inhibited adipogenic differentiation as determined by decreased <jats:italic>PPAR\u03b3<\/jats:italic> expression and reduced intracellular lipid accumulation. Bioinformatic analysis of gene expression profiles demonstrated several involved pathways, including PI3K\/AKT, MAPK, EGFR, and VEGF signaling. 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