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.

抽象的 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）对于体内平衡都至关重要。 RS 辅助气体 细胞呼吸交换，美国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。两者都出现 通过分支形态发生，具有高度血管性，具有大的内皮/上皮/神经 界面，并消除不需要的物质进入外部环境。因此，他们是“障碍” 系统”需要广泛的免疫监视并受到环境、 感染性和炎症性损伤以及纤维化失修。任何一个系统的故障都会导致 治疗费用昂贵的慢性衰弱性疾病。加深对两者的理解 高分辨率、高内容多尺度水平的系统和实质细胞外 空间相互作用将为形态发生、稳态和 身体主要障碍的损伤/修复。表征所有细胞类型的特性和 他们的空间组织是理解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 的空间多组学图 结合高效测序技术，以单细胞分辨率研究屏障器官 分离细胞的方法，以及 RNA 和蛋白质的高度多重原位作图 荧光成像。 我们计划在 4 年资助期内通过三个具体目标来实现这一目标。目标 1. 我们 将建立一个实验和计算管道来生成和分析 3D 多 人体组织的组学图谱。该管道将​​包括单核 RNA 测序和 染色质可及性图谱、RNA 和蛋白质的高度多重原位成像以及 计算框架集成不同类型的数据以创建连贯的空间地图 RNA、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 肺气道和肺前组织图 (LAPMAP)，覆盖整个人体胸腔内 气道，以及两性人类肺部的三个关键生态位。目标 3. 一秒钟内 OSP，我们将创建膀胱输尿管和肾脏图（BUKMAP），涵盖人体肾脏 和下尿路。