Zhang Xinguo, Bai Ruifeng, Li Minjuan, Li Zhigang, Zhao Xian, Cao Renwei, Tan Shen, Cheng Kaiyuan, Zha Yejun, Jiang Xieyuan, Lu Shuai
Department of Orthopedic, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, China.
Department of Clinical Laboratory, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
Front Endocrinol (Lausanne). 2025 May 27;16:1603955. doi: 10.3389/fendo.2025.1603955. eCollection 2025.
To analyze the heterogeneity of parathyroid cells between patients with primary hyperparathyroidism (PHPT) osteoporosis and PHPT non-osteoporosis patients.
Resected parathyroid tissues were collected from PHPT patients of osteoporosis and non-osteoporosis. Single cell sequencing (SCS) to investigate cell types in parathyroid tissue involved in osteoporosis under PHPT. Further cell-cell interaction and communication, pseudotime trajectory analysis, sub-population analysis of parathyroid chief cells and parathyroid oxyphil cells, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional prediction analysis to confirm specific function of parathyroid cells.
Hallmark-IL2/STAT5 and WNT/β-catenin pathways were upregulated in parathyroid cells of osteoporosis patients. Highest interactions and cell-cell communications were enriched in parathyroid cells. Subcluster analysis disclosed overall highest 31.86% CXCL10-PCC parathyroid chief cells, but SPARCL1-OC parathyroid oxyphil cells were higher in osteoporosis patients. Pseudotime trajectory analysis displayed that parathyroid oxyphil cells were in abundance in osteoporosis patients. In total, 281 DEGs involved in kinase activity were identified in osteoporosis patients. Heatmap showed HSPA1A-OC parathyroid oxyphil cells are predominantly involved in numerous and strongest cell interactions. GO and KEGG enrichment revealed PTH, NOTCH, FGF, EGF and CD59 pathways were significantly up-regulated in all parathyroid subpopulations in osteoporosis patients.
Single cell sequencing revealed highest number of parathyroid cells in parathyroid tissue in patients suffering with PHPT osteoporosis. Parathyroid oxyphil cells are predominantly involved in osteoporosis under PHPT.
分析原发性甲状旁腺功能亢进症（PHPT）骨质疏松患者与PHPT非骨质疏松患者甲状旁腺细胞的异质性。
收集PHPT骨质疏松患者和非骨质疏松患者的甲状旁腺切除组织。采用单细胞测序（SCS）研究PHPT情况下甲状旁腺组织中参与骨质疏松的细胞类型。进一步进行细胞间相互作用和通讯、伪时间轨迹分析、甲状旁腺主细胞和甲状旁腺嗜酸性细胞的亚群分析、基因本体论（GO）和京都基因与基因组百科全书（KEGG）功能预测分析，以确认甲状旁腺细胞的特定功能。
骨质疏松患者甲状旁腺细胞中标志性的IL2/STAT5和WNT/β-连环蛋白通路上调。甲状旁腺细胞中富集了最高的相互作用和细胞间通讯。亚群分析显示，总体上最高比例为31.86%的CXCL10-PCC甲状旁腺主细胞，但骨质疏松患者中SPARCL1-OC甲状旁腺嗜酸性细胞比例更高。伪时间轨迹分析显示，骨质疏松患者甲状旁腺嗜酸性细胞数量丰富。共鉴定出281个参与激酶活性的差异表达基因（DEG）。热图显示HSPA1A-OC甲状旁腺嗜酸性细胞主要参与众多且最强的细胞相互作用。GO和KEGG富集分析显示，骨质疏松患者所有甲状旁腺亚群中PTH、NOTCH、FGF、EGF和CD59通路均显著上调。
单细胞测序显示，PHPT骨质疏松患者甲状旁腺组织中甲状旁腺细胞数量最多。甲状旁腺嗜酸性细胞在PHPT导致的骨质疏松中起主要作用。
