Characterization of LGR5- and AMHR2-derived ovarian surface epithelium (OSE) in mice

Autor: Yu-Wen Kao, 高郁雯
Rok vydání: 2019
Druh dokumentu: 學位論文 ; thesis
Popis: 107
Ovarian cancer is the 10th leading cancer-related death in Taiwan in 2016. About 85% of malignant ovarian cancers are epithelial ovarian carcinomas (EOC).However, the cells of origin and pathogenesis of EOC are poorly understood. LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) was previously reported as the marker of stem/progenitor cells in ovary epithelia. In this study, we sorted LGR5-positive (LGR5+) and LGR5-negative (LGR5-) primary OSE populations according to the level of EGFP fluorescence from the Lgr5-EGFP-IRES-CreERT2 mouse ovaries, and further established the monoclonal OSE-sphere formation assays. We found that the expression of LGR5 was approximately 36% among the ovaries and the sphere-forming efficiency of LGR5+ cells was higher than LGR5- cells. Using BrdU pulse-chase method for one day and three months after last injection, we found that the BrdU+ or Ki67+ OSEs in LGR5+ and LGR5- populations showed no obvious difference. This observation indicates that LGR5+ population in OSE might not be the slow-cycling cell. On the other hand, Amhr2 was reported that involved in the development of female reproductive tract. We found that the AMHR2+-derived cells have higher sphere-forming ability than non-AMHR2 cells. Interestingly, we found that all LGR5+ cells were overlapped with AMHR2 lineage population in Lgr5-EGFP-IRES-CreERT2/+;Amhr2-Cre/+;R26R-RFP/+ ovaries. The data suggested Amhr2-expressing cells may possess the capacity for self-renew and generate the progeny in OSE.
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