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

Shuai Lu; Xi Chen; Maoqi Gong; Shuo Chen; Jianyu Zhang; Xigong Zhang; Chengai Wu; Aimin Cui; Xieyuan Jiang

doi:10.3389/fendo.2023.1165890

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

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

Authors

Shuai Lu¹, Xi Chen², Maoqi Gong¹, Shuo Chen¹, Jianyu Zhang¹, Xigong Zhang¹, Chengai Wu³, Aimin Cui³, Xieyuan Jiang¹

Affiliations

¹ Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Beijing, China.
² Department of Adult Joint Reconstructive Surgery, Beijing Jishuitan Hospital, Fourth Clinical College of Peking University, Jishuitan Orthopaedic College of Tsinghua University, Beijing, China.
³ Beijing Institute of Trauma and Orthopedics, Beijing, China.

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.

Keywords: ScRNA-seq; cellular interactions; gene expression; primary hyperparathyroidism; sex difference.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Endothelial Cells / metabolism
Female
Humans
Hyperparathyroidism, Primary* / genetics
Hyperparathyroidism, Primary* / metabolism
Male
Parathyroid Hormone / genetics
Parathyroid Hormone / metabolism
Sequence Analysis, RNA
Sex Characteristics

Substances

Parathyroid Hormone

Grants and funding

This study was supported by National Key R&D Project (2022YFC2407501), Beijing JST Research Funding (ZR-202206), Beijing Municipal Health Commission (BMHC2019-9) and National Key R&D Program of China (2021YFC2501700). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.