摘要Pleomorphic adenoma(PA)is the most common benign tumour in the salivary gland and has high morphological complexity.However,the origin and intratumoral heterogeneity of PA are largely unknown.Here,we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations,three recapitulating the epithelial states of the normal parotid gland,and two PA-specific epithelial cell(PASE)populations unique to tumours.Then,six subgroups of PASE cells were identified,which varied in epithelium,bone,immune,metabolism,stemness and cell cycle signatures.Moreover,we revealed that CD36+ myoepithelial cells were the tumour-initiating cells(TICs)in PA,and were dominated by the PI3K-AKT pathway.Targeting the PI3K-AKT pathway significantly inhibited CD36+ myoepithelial cell-derived tumour spheres and the growth of PA organoids.Our results provide new insights into the diversity and origin of PA,offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.