背景:迄今为止,由于在人类或动物模型中难以获得正常的甲状旁腺样本,我们对这个最后发现的器官的了解仍然有限。
方法:在本研究中,我们使用10×基因组学平台对6个正常甲状旁腺和8个甲状旁腺腺瘤样本进行了单细胞转录组分析.
结果:我们提供了甲状旁腺内分泌细胞的详细表达图谱。有趣的是,我们发现甲状旁腺内分泌细胞中CD4和CD226的异常高表达水平,甚至高于淋巴细胞。甲状旁腺内分泌细胞中淋巴细胞标志物的异常表达与正常甲状旁腺中CD4T细胞的消耗有关。此外,甲状旁腺腺瘤内分泌细胞中CD4和CD226的表达显著降低,这与Treg计数的显着增加有关。最后,沿着发展轨迹,我们发现了POMC的损失,ART5和CES1的表达是甲状旁腺增生的最早标志。
结论:我们建议甲状旁腺内分泌细胞中CD4和CD226表达的缺失,再加上Treg细胞数量的增加,可能与甲状旁腺腺瘤的发病机制有关。我们的数据也为理解CD4分子的非规范功能提供了有价值的信息。
背景:这项工作得到了中国国家重点研发计划(2022YFA0806100)的支持,国家自然科学基金(82130025,82270922,31970636,32211530422),山东省自然科学基金(ZR2020ZD14),济南创新团队(2021GXRC048)和山东第一医科大学优秀人才带动计划和学术促进计划(2019LJ007)。
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.
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: 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).