Epithelial stem cell regulation of pregnancy establishment

项目总结 皮时英在小鼠子宫中发明的遗传单细胞谱系示踪系统被应用于揭示上皮干细胞在动情周期和分娩后支持子宫内膜周期再生。这些数据支持干细胞对维持子宫内环境平衡和功能至关重要的观点。这里的目的是确定上皮干细胞对妊娠形成的调节。哺乳动物子宫的主要功能是为胚胎植入和发育提供最佳的环境。植入是一个精心安排的过程，涉及到接受子宫和有能力的胚胎之间的相互作用。子宫容受性要求子宫内膜上皮细胞增殖，然后对来自卵巢的E2和P4做出反应而分化。在这里，我们假设子宫内膜上皮干细胞在妊娠的建立中是关键的。本申请所采用的研究策略在概念和技术上都是创新的。拟议的研究将填补我们对子宫上皮干细胞生物学的认识的重大空白，成功完成研究有望加快开发个性化的药物方法，以治疗不孕不育相关的子宫内膜疾病和影响妇女生殖健康的疾病。

PROJECT SUMMARY A genetic single-cell lineage tracing system invented by PI Shiying Jin in the mouse uterus has been applied to reveal that epithelial stem cells support endometrial cyclical regeneration during the estrous cycle as well as after parturition. This data supports the idea that stem cells are critically important to maintain uterine homeostasis and function. The objective here is to determine the epithelial stem cell regulation of pregnancy establishment. The main function of the mammalian uterus is to provide an optimal environment for embryo implantation and development. Implantation is a finely orchestrated process that involves interaction between a receptive uterus and competent embryo. Uterine receptivity requires that the endometrial epithelial cells proliferate and then differentiate in response to E2 and P4 from the ovary. Here, we hypothesize that endometrial epithelial stem cells are critical in pregnancy establishment. The research strategy employed in this application is conceptually and technically innovative. The proposed studies will fill a substantial gap in our understanding of the biology of uterine epithelial stem cells, and successful completion is expected to accelerate the development of personalized medicine approaches to treat infertility associated disorders of the endometrium and diseases that impact the reproductive health of women.