The role of ESRRA and JUNB in oxyphil cells: insights from spatial transcriptomics and single-cell transcriptomics in...

Oxyphil cells are a primary cellular component of the parathyroid gland. Due to the limitations of techniques for separating oxyphil cells from chief cells, the characteristics and functions of oxyphil cells in uremic secondary hyperparathyroidism (SHPT) remain largely unclear. Therefore, we integrated spatial transcriptomics and single-cell transcriptomics to investigate the characteristics of oxyphil cells and the association between oxyphil cells and calcitriol resistance in SHPT. 6 uremic SHPT samples and 3 normal parathyroid samples were used for single-cell transcriptomics, while the most suitable SHPT sample was used for spatial transcriptomics. By integrating spatial transcriptomics with single-cell transcriptomics data (93073 cells), we identified a subset of 7653 cells with high confidence as oxyphil cells. Both transcriptomic data indicated a higher mitochondrial transcript proportion in oxyphil cells, and further investigation revealed that the transcription factor estrogen related receptor alpha (ESRRA), participated in mitochondrial biogenesis in these cells. Meanwhile, lower VDR expression and calcitriol resistance were observed in oxyphil cells. Further investigation demonstrated that the transcription factor JUNB promoted the transcription of VDR gene by binding to the promoter area of VDR gene, thus ameliorating calcitriol resistance of oxyphil cells in SHPT. These findings offer reliable evidence and new insights into the characteristics of oxyphil cells and their potential role in SHPT, and provide JUNB as a potential target for calcitriol resistance in SHPT.