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单细胞 RNA 测序揭示了细胞异质性在原发性甲状旁腺功能亢进性别差异中的作用。

Single-cell RNA sequencing reveals the role of cell heterogeneity in the sex difference in primary hyperparathyroidism.

机构信息

Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Beijing, China.

Department of Adult Joint Reconstructive Surgery, Beijing Jishuitan Hospital, Fourth Clinical College of Peking University, Jishuitan Orthopaedic College of Tsinghua University, Beijing, China.

出版信息

Front Endocrinol (Lausanne). 2023 Mar 7;14:1165890. doi: 10.3389/fendo.2023.1165890. eCollection 2023.

DOI:10.3389/fendo.2023.1165890
PMID:36960393
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10028180/
Abstract

OBJECTIVE

To explore the difference in parathyroid tissue-derived cells between male and female PHPT patients.

METHODS

Resected parathyroid tissues were collected from PHPT patients of both sexes. Single cells were isolated and sequenced for RNA expression profiles. The cell sequencing data were annotated by cell type, followed by population analysis, functional analysis, pathway analysis, cell communication analysis, differential gene expression analysis, and pseudotime trajectory analysis. The subcluster analyses were also performed in the parathyroid cells.

RESULTS

No substantial difference in the cell population, function, or communication is found between the two sexes. The interferon-a response, oxidative phosphorylation, and reactive oxygen species pathways are up-regulated in females than in male patients, mainly contributed by fibroblast cells, endothelial cells, parathyroid cells, and myeloid cells, which also have significantly more up-regulated pathways and cellular interactions than the other three cell types. The subcluster analysis of parathyroid cells identified five subpopulations: SPARCL1-OC and ISG15-OC are predominant in females, while more S100A13-PCC and PTHLH-OC are found in males. The cellular functions are also elevated in females compared with males. Cells from female patients show a higher expression level of parathyroid hormone (PTH) but a lower expression level of parathyroid hormone-like hormone (PTHLH). The cell pseudotime trajectory and pathway analyses show that the oxyphil cells may be more mature and functionally active than the chief cells in both sexes.

CONCLUSION

These findings suggest that the sex difference in PHPT may be caused by the differentially expressed genes and activated pathways in different cell types in the parathyroid tissue. The heterogeneity of parathyroid cell subpopulations, especially in oxyphil cells, may be associated with the sex differences in PHPT pathogenesis.

摘要

目的

探索男性和女性 PHPT 患者甲状旁腺组织来源细胞的差异。

方法

收集来自男女 PHPT 患者的甲状旁腺组织。分离并对单细胞进行 RNA 表达谱测序。对细胞测序数据进行细胞类型注释,然后进行群体分析、功能分析、通路分析、细胞通讯分析、差异基因表达分析和伪时间轨迹分析。还对甲状旁腺细胞进行了亚群分析。

结果

两性之间细胞群体、功能或通讯没有明显差异。干扰素-α反应、氧化磷酸化和活性氧物质通路在女性中上调,高于男性患者,主要由成纤维细胞、内皮细胞、甲状旁腺细胞和髓样细胞贡献,这些细胞的上调通路和细胞相互作用也明显多于其他三种细胞类型。甲状旁腺细胞的亚群分析确定了五个亚群:SPARCL1-OC 和 ISG15-OC 在女性中占主导地位,而男性中则发现更多的 S100A13-PCC 和 PTHLH-OC。与男性相比,女性的细胞功能也升高。女性患者的甲状旁腺激素(PTH)表达水平较高,但甲状旁腺素样激素(PTHLH)表达水平较低。细胞伪时间轨迹和通路分析表明,两性中的嗜酸性细胞可能比主细胞更成熟和功能活跃。

结论

这些发现表明,PHPT 的性别差异可能是由甲状旁腺组织中不同细胞类型的差异表达基因和激活通路引起的。甲状旁腺细胞亚群的异质性,特别是嗜酸性细胞,可能与 PHPT 发病机制中的性别差异有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/fc4029a861f6/fendo-14-1165890-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/76f29372f1d2/fendo-14-1165890-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/fe1674e7d0d8/fendo-14-1165890-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/dbdfda02cde2/fendo-14-1165890-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/ced25d01a556/fendo-14-1165890-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/93791c5bbd02/fendo-14-1165890-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/fc4029a861f6/fendo-14-1165890-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/76f29372f1d2/fendo-14-1165890-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/fe1674e7d0d8/fendo-14-1165890-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/dbdfda02cde2/fendo-14-1165890-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/ced25d01a556/fendo-14-1165890-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/93791c5bbd02/fendo-14-1165890-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a01/10028180/fc4029a861f6/fendo-14-1165890-g006.jpg

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