PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE)

摘要 肾脏已经发展出一种复杂的三维结构，以发挥其关键功能，包括 排泄废物，维持液体和盐的内部平衡，控制血压， 和荷尔蒙功能。了解单个肾细胞类型和细胞状态在这些疾病中的作用， 在健康和疾病过程中的关键是开发新的靶向疗法。由此引发的广泛研究 研究小组和其他人已经开始在肾活检组织中鉴定分子疾病机制 并帮助开发新的疾病标志物和治疗方法。通过综合错误的精确医学 肾中RNA（PREMIERE）网络带来了来自三个领先生物医学研究的调查人员 与不同的机构，互补的专业知识在一起。我们的团队在以下方面有着良好的记录： 共同致力于开发肾脏疾病分子分析的最新方法。我们将继续 对来自肾脏的研究活检进行高质量，高通量的单细胞RNA测序 精准医学项目和推进技术，以实现更深的序列覆盖，降低成本， 更小的活检部分，而不会丢失数据，因此可以在KPMP中采用其他技术， 鲁棒和可再现的方式。这些单细胞谱将与患者的疾病状态联系起来。 与特定细胞和疾病相关的关键特征将被提取并定位在空间背景中 使用特定的，高度多重的RNA染色技术。此外，我们还将采用切割 边缘空间转录组学技术，将细胞簇映射到其局部环境，以增加维度 疾病的理解。为此，PREMIERE研究人员将与组织密切合作， 采购网站和KPMP的中央枢纽，利用他们20年的团队科学经验， 在KPMP资助周期结束时，确定了新的细胞类型特异性治疗靶点， 未来的治疗管道。

ABSTRACT The kidney has developed a complex, three-dimensional architecture to serve its key functions, including excretion of waste substances, maintenance of the internal balance for fluid and salt, blood pressure control, and hormonal function. Understanding the roles of the individual renal cell types and cell states in these processes in health and disease is critical to develop novel targeted therapies. Extensive studies lead by this investigative group and others have started to identify molecular disease mechanism in renal biopsy tissues and helped to develop novel disease markers and therapies. The PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE) Network has brought investigators from three leading biomedical research institutions with diverse, complementary expertise together. Our team has an established track record in working jointly to develop state of the art approaches in molecular analysis of renal disease. We will continue to perform high-quality, high-throughput single cell RNA sequencing on research biopsies from the Kidney Precision Medicine Project and advance the technology for deeper sequence coverage, reduce cost, use smaller biopsy portions without data loss so that additional technologies can be employed across KPMP, in a robust and reproducible manner. These single cell profiles will be linked to the disease states of the patients. Key signatures associated with specific cells and diseases will be extracted and localized in the spatial context of the kidney using specific, highly multiplexed RNA staining techniques. Additionally, we will employ cutting edge spatial transcriptomic technology to map cell clusters to their local environment for an added dimension of disease understanding. To this end the PREMIERE investigators will work closely with the tissue procurement sites and the Central Hub of the KPMP, using their 20 years of experience in team science, so that at the end of the KPMP funding cycle, novel cell type specific treatment targets are identified fueling the therapeutic pipelines of the future.