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）和尿液系统 （美国：肾脏，输尿管和膀胱）都对体内平衡至关重要。 RS susters气体 交换细胞呼吸，美国维持液体和电解质平衡， 支持消除有毒物质。它们一起调节酸碱平衡。两者都出现 通过分支形态发生，高度血管，具有较大的内皮/上皮/神经 接口，消除不需要的外部环境。因此，他们是“障碍 需要广泛的免疫手术并受到环境的影响， 传染性和炎症性损伤和纤维化失修。两种系统的故障导致 慢性衰弱的疾病是昂贵的。提高对两者的理解 高分辨率，高含量多尺度和副型细胞的系统 太空相互作用将为形态发生，稳态和 人体主要障碍的伤害/修复。表征所有细胞类型的身份和 他们的空间组织是了解功能和故障的第一步 这些器官。在这个项目中，我们建议构建RS和我们的空间多媒体地图 使用高效测序的单细胞分辨率的屏障器官 分离的细胞的方法，以及高度多路复用的RNA和蛋白质的原位映射 荧光成像。 我们计划在4年的资助期间以三个特定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，用于生成和分析3D多 人类组织的法图。该管道将​​包括单核RNA测序和 染色质可及性映射，高度多路复用的RNA和蛋白质的原位成像，A 计算框架集成了不同类型的数据以创建连贯的空间图 RNA，染色质状态和蛋白质。目标2。在一个特定器官项目（OSP）中，我们将创建 肺气道和原质图（LAPMAP），覆盖整个胸腔内的人 气道以及两个性别的人类肺的三个关键壁ni。目标3。一秒钟 OSP，我们将创建膀胱输尿管和肾脏地图（bukmap），覆盖人类肾脏 并降低尿路。