Unraveling epithelial cell heterogeneity in adamantinomatous craniopharyngioma using single-cell and spatially resolved analysis

Adamantinomatous craniopharyngioma (ACP) is an intractable and histologically complex epithelial neoplasm with variable pathognomonic features, while its cellular composition, particularly the epithelial component, is poorly characterized. Herein, a single-nucleus transcriptome atlas specific to ACP was constructed by performing a single-nucleus RNA sequencing (snRNA-seq) survey of 55967 nuclei in 6 ACP samples from 3 patients. We revealed 6 epithelial subtypes with diverse molecular functions in ACP by integrating snRNA-seq, spatial transcriptomic (ST) and immunostaining data. Additionally, we investigated the potential regulatory mechanism of ACP calcification by performing a trajectory analysis and transcription factor regulon analysis. Finally, we characterized the molecular characteristics of neurons and discovered potential epithelial cell–neuron crosstalk in ACP tissues. Overall, this large-scale single-nucleus atlas combined with ST provides, for the first time, unprecedented insights into epithelial cell heterogeneity within ACP and can serve as a resource for further investigation of tumor dynamics.