Role of Notch pathway in kidney injury

纤维化是慢性肾脏病（CKD）的组织学表现。而 急性肾损伤（阿基）后，肾脏可以完全再生和修复， 反应还可以遵循导致上皮萎缩的纤维化中的适应不良路径， 肌成纤维细胞、胶原和炎性细胞的积聚。 我们对再生和分化的理解进展的一个关键瓶颈是 对细胞特异性基因组范围内基因表达变化的了解有限。一 蜂窝测量技术的革命正在进行中。这是我们第一次 在一个细胞中监测数千个单个细胞的全基因组基因调控的能力， 使用单细胞“组学”研究的单一实验。这些实验使我们能够 发现新的细胞类型和状态，追踪细胞的起源并识别潜在的细胞- 因此，特定基因表达的变化，这种方法将使我们能够了解 纤维化中的修复性和适应不良再生。 该提案的主要目标是探索Notch途径 在慢性肾病和肾纤维化的发展中起重要作用。

Fibrosis is the histological manifestation of chronic kidney disease (CKD). While the kidney can fully regenerate and repair following acute kidney injury (AKI), injury response can also follow a maladapative path in fibrosis resulting in epithelial atrophy, accumulation of myofibroblasts, collagen and inflammatory cells. A key bottleneck to progress in our understanding of regeneration and differentiation has been the limited insight into cell-specific genome wide gene expression changes. A revolution in cellular measurement technology is under way. For the first time, we have the ability to monitor genome-wide gene regulation in thousands of individual cells in a single experiment, using single cell “omic” studies. Such experiments allow us to discover new cell types and states, trace the origin of cells and identify underlying cell- specific gene expression changes therefore, this method shall enable us to understand reparative and maladaptive regeneration in fibrosis. The primary goal of this proposal is to explore the hypothesis that the Notch pathway plays an important role in the development of chronic kidney disease and kidney fibrosis.