基于单细胞解析和类器官模拟的人类成体子宫细胞图谱与内膜分化调控机制研究

人类子宫组织具有周期性完美再生能力和高度可塑性，但大面积、全层性子宫组织修复重建仍面临巨大挑战。类器官技术有望解决该临床难题，而子宫类器官构建的关键人成体子宫干祖细胞亚群特征及与子宫再生微环境互作调控机制尚不明确。基于前期研究本项目拟通过单细胞测序分析技术解析正常人子宫组织细胞图谱，构建子宫干祖细胞亚群及周期性再生微环境互作网络；进一步通过类器官培养技术体外模拟、调控子宫干祖细胞与微环境互作；最终研究体外构建子宫类器官在子宫修复重建的效用。本研究的开展将系统揭示子宫组织干祖细胞微环境及其互作在子宫周期性再生中的规律，形成基于成体人子宫类器官的子宫修复重建新技术。

The human uterus is a highly dynamic tissue that undergoes repeated damage repair and regeneration. However, it's still difficult to repair and reconstruct large scale, full thickness uterine tissues. Organoid technology is promising approach to solve these problems, but the key cell subset of uterine organoid and the regulatory mechanism remains unclear: Endometrial stem progenitor cells were shown to be involved in the regeneration of the damaged functional layer during the menstrual cycle and continuous growth upon embryo implantation. However, the precise identify, function and regulatory mechanisms of the uterus epithelial stem progenitors during the period of adult uterine cyclical repair and regeneration in vivo remains unclear. This project aims to build cell atlas of normal human uterine use single-cell sequencing analysis and reconstruct the interaction network of uterine stem progenitor cell subsets and their microenvironment. Furthermore, techniques of organoid culture is used to mimic and regulate the interaction network of uterine stem progenitor cells. The ultimate goal of this project is the utility of uterus organoid in the uterine repair and reconstruction. The study will systematically reveal the rules of uterine stem progenitor cells, the microenvironment and their interactions in uterine periodic regeneration, and build a new uterine repair and reconstruction technology based on human uterine organoids.