Single-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue

• Published in: Genome research Vol. 34; no. 6; pp. 837 - 850
• Main Authors: Venkat, Aarthi, Carlino, Maximillian J, Lawton, Betty R, Prasad, Manju L, Amodio, Matthew, Gibson, Courtney E, Zeiss, Caroline J, Youlten, Scott E, Krishnaswamy, Smita, Krause, Diane S
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.06.2024
• Subjects: Animals; Cell Communication; Cell interactions; Chemokines - genetics; Chemokines - metabolism; Endothelial cells; Epithelial cells; Epithelial Cells - metabolism; Gene Expression Profiling - methods; Humans; Macaca mulatta; Microenvironments; Parathyroid Glands - metabolism; Parathyroid hormone; Parathyroid Hormone - genetics; Parathyroid Hormone - metabolism; Progenitor cells; Single-Cell Analysis - methods; Transcription, Genetic; Transcriptome; Transcriptomes; Transcriptomics
• ISSN: 1088-9051; 1549-5469; 1549-5469
• DOI: 10.1101/gr.278215.123

Studies on human parathyroids are generally limited to hyperfunctioning glands owing to the difficulty in obtaining normal human tissue. We therefore obtained non-human primate (NHP) parathyroids to provide a suitable alternative for sequencing that would bear a close semblance to human organs. Single-cell RNA expression analysis of parathyroids from four healthy adult reveals a continuous trajectory of epithelial cell states. Pseudotime analysis based on transcriptomic signatures suggests a progression from progenitors to mature parathyroid hormone ( )-expressing epithelial cells with increasing core mitochondrial transcript abundance along pseudotime. We sequenced, as a comparator, four histologically characterized hyperfunctioning human parathyroids with varying oxyphil and chief cell abundance and leveraged advanced computational techniques to highlight similarities and differences from non-human primate parathyroid expression dynamics. Predicted cell-cell communication analysis reveals abundant endothelial cell interactions in the parathyroid cell microenvironment in both human and NHP parathyroid glands. We show abundant transcripts in both human adenoma and normal primate parathyroid cells and use coimmunostaining to reveal high levels of RARRES2 protein (also known as chemerin) in PTH-expressing cells, which could indicate that RARRES2 plays an unrecognized role in parathyroid endocrine function. The data obtained are the first single-cell RNA transcriptome to characterize nondiseased parathyroid cell signatures and to show a transcriptomic progression of cell states within normal parathyroid glands, which can be used to better understand parathyroid cell biology.