Single-cell profiling of mouse and primate ovaries identifies high levels of EGFR for stromal cells in ovarian aging

Ye Wei; Ruidi Yu; Sheng Cheng; Ping Zhou; Shaomei Mo; Chao He; Chang Deng; Peng Wu; He Liu; Canhui Cao

doi:10.1016/j.omtn.2022.11.020

Single-cell profiling of mouse and primate ovaries identifies high levels of EGFR for stromal cells in ovarian aging

Mol Ther Nucleic Acids. 2022 Nov 25:31:1-12. doi: 10.1016/j.omtn.2022.11.020. eCollection 2023 Mar 14.

Authors

Ye Wei¹, Ruidi Yu¹, Sheng Cheng^{1

2}, Ping Zhou³, Shaomei Mo^{4

5}, Chao He¹, Chang Deng¹, Peng Wu⁶, He Liu⁴, Canhui Cao^{1

4

3}

Affiliations

¹ Department of Gynecology and Obstetrics, Key Laboratory of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
² National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070, China.
³ Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
⁴ Department of Gastrointestinal Surgery, Reproductive Research Institute, Peking University Shenzhen Hospital, Guangdong 518036, China.
⁵ The Fifth Clinical College, Anhui Medical University, Hefei 230000, China.
⁶ Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Abstract

Increased ovarian fibrosis and an expanded stromal cell compartment are the main characteristics of aging ovaries. However, the molecular mechanisms and the key factor of stromal cells underlying ovarian aging remain unclear. Here, we explored single-cell transcriptomic data of ovaries from the adult mouse (4,363 cells), young (1,122 cells), and aged (1,479 cells) non-human primates (NHPs) to identify expression patterns of stromal cells between young and old ovaries. An increased number of stromal cells (p = 0.0386) was observed in aged ovaries of NHPs, with enrichment processes related to the collagen-containing extracellular matrix. In addition, differentially expressed genes of stromal cells between young and old ovaries were regulated by ESR1 (p = 7.94E-08) and AR (p = 1.99E-05). Among them, EGFR was identified as the common target and was highly expressed (p = 7.69E-39) in old ovaries. In human ovaries, the correlated genes of EGFR were associated with the process of the cell-substrate junction. Silencing of EGFR in human ovarian stromal cells led to the reduction of cell-substrate junction via regulating phosphorylation modification of the AKT-mTOR signaling pathway and stromal cell marker genes. Overall, we identified high levels of EGFR for stromal cells in ovarian aging, which provides insight into the cell type-specific molecular mechanisms underlying ovarian aging at single-cell resolution.

Keywords: EGFR; MT: Bioinformatics; ovarian aging; single-cell transcriptomic analysis; stromal cells.