KULMAP: Human Kidney, urinary tract and lung mapping center

摘要 呼吸系统（RS：肺气道和肺泡实质）和泌尿系统 (US肾脏、输尿管和膀胱）对于体内平衡都是至关重要的。RS节省了天然气 交换细胞呼吸和US维持液体和电解质平衡， 支持消除有毒物质。它们共同调节酸碱平衡。两者都产生 通过分支形态发生，高度血管化，具有大的内皮/上皮/神经 界面，并消除不需要的物质到外部环境。因此，它们是“屏障 系统”需要广泛的免疫监视， 感染性和炎性损伤以及纤维化破损。任何一个系统的故障都会导致 慢性衰弱性疾病的治疗成本很高。加深对两者的了解 系统在高分辨率，高内容的多尺度水平和薄壁细胞外 空间相互作用将提供对形态发生、体内平衡和 损伤/修复身体的主要屏障。表征所有细胞类型的身份， 它们的空间组织是理解其功能和故障的第一步 这些器官。在这个项目中，我们建议建立RS和US的空间多组学地图 单细胞分辨率的屏障器官，使用高效测序的组合 方法解离的细胞，和高度多重原位定位的RNA和蛋白质， 荧光成像 我们计划在4年的资助期内通过三个具体目标实现这一目标。目标1.我们 将建立一个实验和计算管道，用于生成和分析3D多 人类组织的组学图谱。该管道将包括单核RNA测序和 染色质可及性作图，RNA和蛋白质的高度多重原位成像，以及 计算框架，以整合不同类型的数据， RNA、染色质状态和蛋白质。目标2.在一个器官特异性项目（OSP）中，我们将创建 肺气道和实质标测图（LAPMAP），覆盖整个胸内人体 呼吸道，以及两种性别的人肺的三个关键小生境。目标3：在第二 OSP，我们将创建膀胱输尿管和肾脏地图（BUKMAP），涵盖人类肾脏 和下尿路。

Abstract The respiratory system (RS: lung airways and alveolar parenchyma) and the urinary system (US:kidney, ureters and bladder) are both critical to homeostasis. The RS subserves gas exchange for cellular respiration and the US maintains fluid and electrolyte balance and supports elimination of toxic substances. Together, they regulate acid-base balance. Both arise via branching morphogenesis, are highly vascular, with a large endothelial/epithelial/neural interface, and eliminate unwanted substance to the outside environment. They are thus “barrier systems” that require extensive immune surveillance and are subject to environmental, infectious and, inflammatory injury, and fibrotic disrepair. Failure of either systems results in chronic debilitating diseases that are costly to manage. Improved understanding of both systems at a high-resolution, high content multiscale level and the parenchymal-extra cellular space interactions will provide remarkable insight into morphogenesis, homeostasis and injury/repair of the body’s principal barriers. Characterizing the identities of all the cell types and their spatial organization is the first step towards understanding the functions and malfunctions of these organs. In this project we propose to build spatial multi-omics maps of RS and US barrier organs at single-cell resolution, using a combination of highly efficient sequencing approach on dissociated cells, and highly multiplexed in situ mapping of RNA and proteins with fluorescent imaging. We plan to accomplish this goal with three specific aims in a 4-year funded period. Aim 1. We will establish an experimental and computation pipeline for generating and analyzing 3D multi- omics maps for human tissues. This pipeline will include single-nucleus RNA sequencing and chromatin accessibility mapping, highly multiplexed in situ imaging of RNA and proteins, and a computational framework to integrate different types of data to create coherent spatial maps of RNA, chromatin status and proteins. Aim 2. In one Organ Specific Project (OSP), we will create a Lung Airways and Prenchymal Map (LAPMAP), covering the entire intrathoracic human airway, as well as three critical niches of the human lung for both sexes. Aim 3. In a second OSP, we will create the Bladder Ureter and Kidney Maps (BUKMAP), covering human kidney and lower urinary tract.