Role of Notch pathway in kidney injury

纤维化是慢性肾脏病(CKD)的组织学表现。而当 急性肾损伤(AKI)后肾脏可完全再生和修复 在导致上皮萎缩的纤维化中，反应也可能沿着不适应的路径进行， 肌成纤维细胞、胶原和炎性细胞积聚。 我们对再生和分化的理解取得进展的一个关键瓶颈是 对细胞特定基因组范围的基因表达变化的洞察有限。一个 细胞测量技术的革命正在进行中。第一次，我们有了 在数以千计的单个细胞中监控全基因组基因调控的能力 单细胞实验，使用单细胞“基因组”研究。这样的实验使我们能够 发现新的细胞类型和状态，追踪细胞的来源，并识别潜在的细胞- 因此，这种方法将使我们能够了解特定基因表达的变化 纤维化中的修复性和适应不良的再生。 这项提议的主要目标是探索Notch途径的假设 在慢性肾脏疾病和肾脏纤维化的发展中起着重要作用。

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.