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

摘要 肾脏已经形成了一个复杂的三维结构来服务于它的关键功能，包括 排泄废物，维持体内水盐平衡，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过程中的作用 健康和疾病的过程对于开发新的靶向治疗至关重要。由此引发的广泛研究 研究小组和其他人已经开始确定肾活检组织中的分子疾病机制 并帮助开发了新的疾病标志物和治疗方法。审问中的精准医学 肾脏中的RNA(首播)网络带来了来自三个领先生物医学研究的研究人员 具有不同、互补专业知识的机构在一起。我们的团队在以下方面有既定的记录 共同开发肾脏疾病分子分析的最新方法。我们将继续 对肾脏的研究活检组织进行高质量、高通量的单细胞RNA测序 精准医疗工程和推进技术，实现更深层次的序列覆盖，降低成本，使用 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 健壮和可重现的方式。这些单细胞图谱将与患者的疾病状态联系在一起。 与特定细胞和疾病相关联的关键特征将被提取并定位在空间上下文中 使用特定的、高度多样化的RNA染色技术对肾脏进行检测。此外，我们将采用切割 边缘空间转录技术，将细胞集群映射到其本地环境，以增加维度 对疾病的理解。为此，首映调查人员将与组织密切合作 采购站点和KPMP的中心中心，利用他们在团队科学方面的20年经验，因此 在KPMP筹资周期结束时，确定了新的细胞类型特异性治疗靶点，从而促进了 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.