本项目将全景式绘制肾脏再生修复过程中肾小管上皮细胞染色质重塑的动态调控网络，深入解码肾脏再生修复过程表观遗传及分子网络机制。肾脏受损后，肾小管细胞通过去分化、增殖、再分化等一系列细胞属性的演变，决定再生修复的结局。但由于肾脏结构的复杂性及以往技术的限制，对于肾脏再生修复的细胞属性演变过程及分子调控网络的深入机制研究很缺乏，对于肾脏再生修复的机制了解不足，临床上缺乏对肾脏损伤有效的干预策略。本项目将以损伤后肾小管上皮细胞为研究对象，采用基于少量细胞的ATAC-seq、组蛋白修饰ChIP-seq、RNA-seq和转录因子CUT&RUN等前沿技术手段，结合生物信息学分析策略，全面解析表观遗传动态调控网络在肾脏再生修复过程中的作用及机制，鉴定损伤修复过程新的生物标志物及治疗干预靶点。在解析机制的基础上，本项目还将利用纳米递送系统，特异性靶向潜在干预靶点，建立促进肾脏再生修复的有序调控和干预新策略。

This project aims to map the dynamic chromatin landscapes in renal tubular epithelial cells during kidney repair and regeneration, and deeply decode the epigenetic and molecular regulatory networks in these processes. Renal tubular epithelial cells are the key cells in renal repair and regeneration. After kidney damage, renal tubular epithelial cells undergo a series of cell fate transition such as dedifferentiation, proliferation and re-differentiation, which ultimately determines the outcome of repair and regeneration. However, due to the complexity of renal structure and technical limitations, the dynamics of cell fate transition and molecular mechanisms of renal repair and regeneration are still unclear, and there is a lack of effective interventions for renal injury in clinical practice. In this project, we plan to systematically profile the transcriptome, dynamic chromatin state and accessibility of renal tubular epithelial cells during kidney repair and regeneration. By using recently developed Low Cell ChIP-seq, ATAC-seq, RNA-seq, and CUT&RUN assays, we aim to establish the epigenetic and molecular regulatory networks in kidney repair and regeneration, and identify new biomarkers and therapeutic targets for renal injuries. Furthermore, we will further explore the use of nanomaterial delivery systems to target potential intervention targets and establish new strategies for orderly regulating and promoting kidney repair and regeneration.