CD24: a marker of granulosa cell subpopulation and a mediator of ovulation

• Published in: Cell death & disease Vol. 10; no. 11; pp. 791 - 12
• Main Authors: Dong, Jun-Peng, Dai, Zhi-Hui, Jiang, Zhong-Xin, He, Yi, Wang, Liang, Liao, Qiu-Ying, Sun, Ning-Xia, Wang, Yi-Ning, Sun, Shu-Han, Lin, Wei, Li, Wen, Yang, Fu
• Format: Journal Article
• Language: English
• Published: England Springer Nature B.V 17.10.2019; Nature Publishing Group UK
• Subjects: Animals; CD24 Antigen - biosynthesis; CD24 Antigen - genetics; CD24 Antigen - metabolism; Cell Line; Chorionic gonadotropin; Chorionic Gonadotropin - pharmacology; Cumulus Cells - cytology; Cumulus Cells - metabolism; Cumulus Cells - physiology; Epidermal growth factor receptors; Female; Follicles; Gene expression; Gonadotropins; Granulosa cells; Granulosa Cells - cytology; Granulosa Cells - metabolism; Granulosa Cells - physiology; Humans; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Organic Anion Transporters; Ovulation; Ovulation - drug effects; Ovulation - physiology; Pituitary (anterior); Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Prostaglandin synthase; Prostaglandin-Endoperoxide Synthases - metabolism; Therapeutic applications
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-1995-1

Granulosa cells (GCs) play a critical role in driving the formation of ovarian follicles and building the cumulus-oocyte complex surrounding the ovum. We are particularly interested in assessing oocyte quality by examining the detailed gene expression profiles of human cumulus single cells. Using single-cell RNAseq techniques, we extensively investigated the single-cell transcriptomes of the cumulus GC populations from two women with normal ovarian function. This allowed us to elucidate the endogenous heterogeneity of GCs by uncovering the hidden GC subpopulation. The subsequent validation results suggest that CD24(+) GCs are essential for triggering ovulation. Treatment with human chorionic gonadotropin (hCG) significantly increases the expression of CD24 in GCs. CD24 in cultured human GCs is associated with hCG-induced upregulation of prostaglandin synthase (ARK1C1, PTGS2, PTGES, and PLA2G4A) and prostaglandin transporter (SLCO2A1 and ABCC4) expression, through supporting the EGFR-ERK1/2 pathway. In addition, it was observed that the fraction of CD24(+) cumulus GCs decreases in PCOS patients compared to that of controls. Altogether, the results support the finding that CD24 is an important mediator of ovulation and that it may also be used for therapeutic target of ovulatory disorders.