Tumour microenvironment has been recognized as a crucial factor influencing disease progression. However, relevant features and functions are insufficiently understood in parathyroid neoplasia. Single-cell RNA sequencing was performed to profile the transcriptome of 27,251 cells from 4 parathyroid adenoma (PA) tissue samples. External transcriptomic datasets and immunofluorescence staining of a tissue microarray were set for expression validation. Eight major cell types and various subpopulations were finely identified in PA. We found that a subcluster of tumour endocrine cells with low copy number variation probably presented as a resting state. Diverse infiltrating immune cell subtypes were identified, constructing an immunosuppressive microenvironment. Tumour-associated macrophages, which indicated an anti-inflammatory phenotype, were significantly increased in PA. Inflammatory tumour-associated fibroblasts (iTAFs) were newly verified and highlighted on the role of stromal-immune crosstalk. Positive correlation between iTAFs and increased CD163+ macrophages was uncovered. Moreover, CXCL12 receptor signalling is important for tumour angiogenesis and immune infiltration. Our findings provide a comprehensive landscape interpreting tumour cell heterogeneity, cell diversity, and immune regulation in parathyroid neoplasia. The valuable resources may promote the understanding of parathyroid tumour microenvironment. Keywords: cell diversity; parathyroid tumour; single-cell RNA sequencing; tumour-associated fibroblast; tumour-associated macrophage.

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