High lymphocyte signature genes expression in parathyroid endocrine cells and its downregulation linked to tumorigenesisResearch in context
Chong Geng,
Junjun Liu,
Bingzhou Guo,
Kailin Liu,
Pengfei Gong,
Bao Wang,
Qiang Wan,
Liang Sun,
Jiajun Zhao,
Yongfeng Song
Affiliations
Chong Geng
Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324 Jingwu Road, Jinan, Shandong 250021, China
Junjun Liu
Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Jinan, Shandong 250013, China; Shandong Institute of Endocrine and Metabolic Diseases, Shandong First Medical University, No.324 Jingwu Road, Jinan, Shandong 250021, China
Bingzhou Guo
College of Artificial Intelligence and Big Data for Medical Sciences, Shandong First Medical University, No.6699 Qingdao Road Jinan, Shandong 250021, China
Kailin Liu
Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324 Jingwu Road, Jinan, Shandong 250021, China
Pengfei Gong
College of Artificial Intelligence and Big Data for Medical Sciences, Shandong First Medical University, No.6699 Qingdao Road Jinan, Shandong 250021, China
Bao Wang
Shandong Institute of Endocrine and Metabolic Diseases, Shandong First Medical University, No.324 Jingwu Road, Jinan, Shandong 250021, China
Qiang Wan
Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Jinan, Shandong 250013, China; Corresponding authors.
Liang Sun
College of Artificial Intelligence and Big Data for Medical Sciences, Shandong First Medical University, No.6699 Qingdao Road Jinan, Shandong 250021, China; Corresponding author.
Jiajun Zhao
Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324 Jingwu Road, Jinan, Shandong 250021, China; Shandong Clinical Research Center of Diabetes and Metabolic Diseases, No.324 Jingwu Road, Jinan, Shandong 250021, China; Shandong Institute of Endocrine and Metabolic Diseases, Shandong First Medical University, No.324 Jingwu Road, Jinan, Shandong 250021, China; Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, No.324 Jingwu Road, Jinan, Shandong 250021, China; Corresponding authors. Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No.324 Jingwu Road, Jinan, Shandong 250021, China.
Yongfeng Song
Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Jinan, Shandong 250013, China; Shandong Clinical Research Center of Diabetes and Metabolic Diseases, No.324 Jingwu Road, Jinan, Shandong 250021, China; Shandong Institute of Endocrine and Metabolic Diseases, Shandong First Medical University, No.324 Jingwu Road, Jinan, Shandong 250021, China; Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, No.324 Jingwu Road, Jinan, Shandong 250021, China; Corresponding author. Department of Endocrinology, Jinan Central Hospital Affiliated to Shandong First Medical University, No.105 Jiefang Road, Jinan, Shandong 250013, China.
Summary: Background: To date, because of the difficulty in obtaining normal parathyroid gland samples in human or in animal models, our understanding of this last-discovered organ remains limited. Methods: In the present study, we performed a single-cell transcriptome analysis of six normal parathyroid and eight parathyroid adenoma samples using 10 × Genomics platform. Findings: We have provided a detailed expression atlas of parathyroid endocrine cells. Interestingly, we found an exceptional high expression levels of CD4 and CD226 in parathyroid endocrine cells, which were even higher than those in lymphocytes. This unusual expression of lymphocyte markers in parathyroid endocrine cells was associated with the depletion of CD4 T cells in normal parathyroid glands. Moreover, CD4 and CD226 expression in endocrine cells was significantly decreased in parathyroid adenomas, which was associated with a significant increase in Treg counts. Finally, along the developmental trajectory, we discovered the loss of POMC, ART5, and CES1 expression as the earliest signature of parathyroid hyperplasia. Interpretation: We propose that the loss of CD4 and CD226 expression in parathyroid endocrine cells, coupled with an elevated number of Treg cells, could be linked to the pathogenesis of parathyroid adenoma. Our data also offer valuable information for understanding the noncanonical function of CD4 molecule. Funding: This work was supported by the National Key R&D Program of China (2022YFA0806100), National Natural Science Foundation of China (82130025, 82270922, 31970636, 32211530422), Shandong Provincial Natural Science Foundation of China (ZR2020ZD14), Innovation Team of Jinan (2021GXRC048) and the Outstanding University Driven by Talents Program and Academic Promotion Program of Shandong First Medical University (2019LJ007).
