Synthesis of the Multi-Modality High Resolution 3-D Atlas of Human Lung

人肺多模态高分辨率 3D 图谱的合成

• 批准号: 10689260
• 负责人: GLORIA S PRYHUBER
• 金额: $ 191.44万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10689260
• 关键词: 3-Dimensional; ATAC-seq; Adult; Age; Alveolar; Alveolar Duct; Anatomy; Atlases; Biodiversity; Biological Assay; Biological Markers; Biology; Bronchioles; Cell Nucleus; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Chemicals; Chromosome Mapping; Collaborations; Communities; Consensus; Data; Data Set; Distal; Equilibrium; Gene Expression; Generations; Genes; Genome; Genomics; Goals; Human; Human BioMolecular Atlas Program; Image; Imaging technology; Immune system; Immunofluorescence Immunologic; In Situ; Individual; Infrastructure; International; Intrapulmonary Bronchus; Investigation; Leadership; Lipids; Lung; Lung diseases; Lymphatic System; Maps; Mass Spectrum Analysis; Methods; Microdissection; Microscopy; Molecular; Morphology; Nature; Nervous System; Nomenclature; Organ; Organ Transplantation; Patient Self-Report; Phase; Pleural; Positioning Attribute; Post-Translational Protein Processing; Proteins; Proteome; Race; Raman Spectrum Analysis; Recovery; Reproducibility; Resolution; Respiratory System; Role; Sampling; Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectrum Analysis; Standardization; Structure; Structure of parenchyma of lung; Techniques; Technology; Terminal Bronchiole; Thick; Three-Dimensional Imaging; Tissue Microarray; Tissue Sample; Tissue imaging; Tissues; Trachea; Variant; Vascular System; advanced analytics; biobank; bronchial artery; cell type; epigenome; epigenomics; genome sequencing; improved; innovation; interest; lung injury; metabolome; metabolomics; molecular imaging; multi-scale atlas; multimodality; multiple omics; novel; preservation; programs; pulmonary function; reconstruction; repaired; respiratory; sex; tissue mapping; transcriptome; transcriptomics; whole genome

Project Summary/Abstract Organ Specific Project Component Multi-Scale Multi-Modality High Resolution Mapping of the Adult Human Lung Maintaining normal lung function and inducing repair of damaged lung can be markedly improved if we better understand the cellular and molecular complexities of the organ. Technical and analytical advances now make it possible to gain detailed access to previously hidden fundamentals of lung biology by generating high resolution, single cell and subcellular, biomolecular maps coalesced into an atlas of the human respiratory system. It is the goal of HuBMAP and specifically of this Lung TMC to generate interactive, searchable, cell type and subtype annotated maps and tabular data representing transcriptome, proteome, metabolome, and select posttranslational modifications (PTMs) of healthy lung. Ultimate deliverable will be integration of these maps into a reference atlas of healthy lung to which diseased lung can be compared. Such a biomolecular atlas with multi- scale, 3D spatial resolution will be truly transformative for human pulmonary biology with ramifications also for understanding the immune and vascular systems throughout the body. Building upon our successful HuBMAP Phase 1 engagement, our tissue mapping strategy brings multiple strengths including 1) an established, robust, tissue biorepository, 2) well oriented tissue samples representing the entire human lung with focus on regions of interest, 3) snRNAseq/ATACseq dual-omic sequencing and mass spectroscopy based bulk metabolomics to provide basis for deconvolution of, 4) novel spatial transcriptomic methods, 5) spatial highly-multiplexed chemical and immunofluorescent microscopy, 5) a suite of unbiased mass spectrometry, stimulated Raman spectroscopy and advanced microscopy technologies, all combined in such a way to enable spatially resolved co-localized 2D and 3D mapping of gene expression, metabolites, lipids, proteins, and protein modifications across lung tissues with single-cell or near single-cell resolution. We will include assays on 40 diverse donor lungs creating tissue microarrays to enhance assay throughput. We envision achieving an unprecedented level of biomolecular mapping of the trachea, extra and intra-pulmonary bronchi with bronchial artery and lymphatic systems, several levels of bronchioles with focus on broncho-vascular bundles and terminal-respiratory-alveolar duct transition regions as well as alveolar and pleural regions. Working with the HuBMAP HIVE and our DAC, our achievable goal will be, by microdissection, serial section reconstruction and 3D imaging of thick sections, a Multi-Scale Multimodality High Resolution 3-D and Tabular Atlas of the Adult Human Lung.

项目摘要/摘要 器官特定项目组件 成人人肺的多尺度多模式高分辨率映射 如果我们更好 了解器官的细胞和分子复杂性。技术和分析进步现在 通过产生较高的 分辨率，单细胞和亚细胞的生物分子图合并为人呼吸道的地图集 系统。它是Hubmap的目标，特别是该肺TMC的目的是生成交互式，可搜索的细胞类型 以及代表转录组，蛋白质组，代谢组的亚型注释图和表格数据，然后选择 健康肺的翻译后修饰（PTMS）。最终可交付的将是将这些地图整合到 可以比较患病肺的健康肺的参考地图集。如此的生物分子地图集 规模，3D空间分辨率将真正对人类肺部生物学具有真正的变革性，并将其分辨出来。 了解整个身体的免疫和血管系统。在我们成功的hubmap基础上建立 1阶段参与，我们的组织映射策略带来了多种优势，包括1）建立，健壮的， 组织生物位，2）代表整个人类肺的定向良好的组织样品，重点是 感兴趣，3）SNRNASEQ/ATACSEQ双 - OMIC测序和基于质谱的批量代谢组学 提供对卷积的基础，4）新型的空间转录方法，5）空间高度多形化学 和免疫荧光显微镜，5）一套无偏的质谱法，刺激的拉曼光谱法 和高级显微镜技术，所有这些都以这种方式合并，以实现空间分辨共定位的2D 以及基因表达，代谢产物，脂质，蛋白质和蛋白质修饰的3D映射 具有单细胞或接近单细胞分辨率。我们将在40种不同的供体肺部进行测定 微阵列增强测定吞吐量。我们设想实现前所未有的生物分子水平 带支气管动脉和淋巴系统的气管，额外和肺内支气管的映射，几个 支气管的水平，重点是支气管 - 血管束和末端 - 呼吸肺泡过渡 区域以及肺泡和胸膜区域。与Hubmap Hive和我们的DAC合作，我们可以实现的 目标将通过微分解，串行部分重建和厚部分的3D成像，一个多尺度 多模式高分辨率3-D和成年人类肺的表格图。