KULMAP: Human Kidney, urinary tract and lung mapping center

KULMAP：人类肾脏、泌尿道和肺部绘图中心

• 批准号: 10237122
• 负责人: James S. Hagood
• 金额: $ 184.85万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-25 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10237122
• 关键词: Acid-Base Equilibrium; Acute; Adult; Alveolar; Anatomy; Area; Bioinformatics; Bladder; Blood Vessels; Cell Nucleus; Cell Respiration; Cells; Chromatin; Chronic; Collaborations; Computer software; Cost of Illness; Data; Development; Electrolyte Balance; Endothelium; Environment; Epithelial; Failure; Fluid Balance; Funding; Gases; Goals; Homeostasis; Human; Human BioMolecular Atlas Program; Image; Immunologic Surveillance; In Situ; Inflammatory; Injury; International; Kidney; Lead; Length; Lower urinary tract; Lung; Lung diseases; Maps; Methods; Molecular; Morphogenesis; Organ; Pathology; Phenotype; Physiology; Poison; Proteins; Pulmonary Pathology; RNA; Regulation; Research Personnel; Resolution; Respirators; Respiratory System; Seasons; System; The Sun; Three-dimensional analysis; Transcript; United States National Institutes of Health; Universities; Ureter; Urinary system; Urinary tract; Visualization; Washington; cell type; computational pipelines; computer framework; experience; fluorescence imaging; human disease; human tissue; improved; in situ imaging; injury and repair; insight; lung development; medical schools; multiple omics; nephrogenesis; open source; relating to nervous system; sex; single cell sequencing; transcriptome; transcriptome sequencing; young adult

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.

摘要 呼吸系统(RS：肺气道和肺泡实质)和泌尿系统 (美国：肾脏、输尿管和膀胱)都是动态平衡的关键。RS服务于天然气 交换细胞呼吸和美国维持液体和电解质平衡和 支持消除有毒物质。它们共同调节酸碱平衡。两者都出现了 通过分支形态发生，是高度血管化的，具有大的内皮/上皮/神经 接口，并消除外界环境中不需要的物质。因此，他们是“屏障” 需要广泛的免疫监视并受环境影响的系统， 感染性和炎症性损伤，纤维性年久失修。任何一个系统的故障都会导致 管理成本高昂的慢性衰弱疾病。提高对两者的理解 高分辨率、高内容的多尺度系统和实质-超细胞 空间相互作用将提供对形态发生、动态平衡和 损伤/修复身体的主要屏障。表征所有细胞类型的身份，并 它们的空间组织是了解功能和故障的第一步 这些器官的。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 分离细胞的方法，以及RNA和蛋白质的高度多重原位定位 荧光成像。 我们计划在四年的资金期限内实现这一目标，并实现三个具体目标。目标1.我们 将建立一条生成和分析3D多维图形的实验和计算流水线 人体组织的组学图谱。这条管道将包括单核RNA测序和 染色质可及性图谱，RNA和蛋白质的高度多重原位成像，以及 集成不同类型数据以创建连贯的空间地图的计算框架 核糖核酸、染色质状态和蛋白质。目标2.在一个器官特定项目(OSP)中，我们将创建 覆盖整个胸腔内人的肺气道和肺前叶地图(LAPMAP) 呼吸道，以及人类肺部的三个关键的利基位置，无论男女。目标3.在一秒钟内 OSP，我们将创建膀胱输尿管和肾脏地图(BUKMAP)，覆盖人类肾脏 和下尿路。