LungMap Phase II - Building a multidimensional map of developing human lung

LungMap 第二阶段 - 构建人类肺部发育的多维图

• 批准号: 10227695
• 负责人: Jeffrey A Whitsett
• 金额: $ 89.73万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-23 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10227695
• 关键词: 3-Dimensional; Acinus organ component; Affect; Algorithms; Alveolar; Anatomy; Atlases; Bioinformatics; Blood Vessels; Carbon Dioxide; Cell Nucleus; Cell model; Cell physiology; Cells; Child; Chromatin; Code; Communities; Complex; Confocal Microscopy; Congenital Disorders; DNA; Data; Data Analyses; Data Coordinating Center; Data Display; Defect; Development; Digestion; Disease; Distal; Doctor of Medicine; Endothelium; Epigenetic Process; Fibroblasts; Gases; Gene Expression; Genetic Diseases; Genetic Transcription; Genomics; Gland; Goals; Health Services Research; Human; Image; Image Analysis; Immune; Immunofluorescence Immunologic; In Situ; In Situ Hybridization; Individual; Infant; Internet; Intuition; Life; Link; Lobule; Location; Lung; Lung diseases; Maps; Mediating; Molecular; Morphogenesis; Mus; Normal tissue morphology; Nuclear; Nuclear RNA; Online Systems; Ontology; Organ; Oxygen; Pathogenesis; Patients; Perinatal; Phase; Physiological; Positioning Attribute; Premature Infant; Protein Isoforms; Proteins; Proteomics; RNA; RNA Probes; RNA Splicing; RNA analysis; Research; Resolution; Role; Science; Signal Transduction; Site; Structure; Structure of parenchyma of lung; Technology; Tissue Procurements; Tissues; Trachea; Visualization; Work; XCL1 gene; analysis pipeline; bioinformatics pipeline; cell type; central database; confocal imaging; data access; data visualization; design; diverse data; droplet sequencing; epigenomics; experience; genetic signature; high resolution imaging; high throughput technology; human data; human tissue; image processing; image reconstruction; indexing; insight; lipidomics; lung acinus structure; lung development; lung imaging; member; multidimensional data; multiple omics; new technology; organ growth; postnatal; preservation; programs; pulmonary function; reconstruction; scaffold; tool; transcriptome sequencing; transcriptomics; two-dimensional; user-friendly; web portal; web services; web site

ABSTRACT Building a Multidimensional Map of Developing Human Lung – Jeffrey A. Whitsett, M.D. PI Our LungMAP2 project seeks to work in a collaborative consortium to develop operational pipelines to study human lung development from the saccular, alveolar stages of morphogenesis at single cell level of resolution. The project will integrate single cell transcriptomic, chromatin accessibility, 2D and 3D high-resolution confocal microscopy, immunofluorescence, multiprobe RNA in situ hybridization studies to create a detailed molecular map of the cells, cell-cell and cell scaffold interactions in their precise anatomic positions in the developing human lung. Our LungMAP2 Center will work in close concert with the Data Coordinating Center (DCC), other LungMAP2 Centers and the Human Tissue Procurement Core (HTPC) to obtain, annotate, preserve and store human tissues using optimal conditions for imaging and omics analyses. Our LungMAP2 project will produce a detailed structural expression atlas of multiple regions, niches in the human lung. We will develop and validate new technologies for tissue clearing, 3D reconstructions of high-resolution images, multi-probe RNA and IF analysis. We will develop new tissue digestion single cell and single nuclear RNA analyses for precise regional niches of the normal developing human lung, tissue from and in infants with rare congenital lung disorders. We will work in a Consortium to develop useful bioinformatic programs, modeling cell-cell, cell matrix interactions to define the signaling and transcriptional programs building and maintaining organ structure and function. Working with the DCC and other LungMAP2 Centers, our bioinformatics pipelines will enable data visualization, interrogation in user friendly web portals for sharing with members of the LungMAP2 Consortium, the DCC and for the research community in general.

摘要 构建人类肺发育的多维地图--Jeffrey A.Whitsett，M.D.Pi 我们的LongMAP2项目寻求在一个协作联盟中工作，以开发运营管道来 从单细胞水平的形态发生的囊状、肺泡期研究人的肺发育 决心的力量。该项目将整合单细胞转录、染色质可及性、2D和3D 高分辨率共聚焦显微镜、免疫荧光、多探针RNA原位杂交研究 要创建细胞、细胞间和细胞支架相互作用的详细分子图谱 发育中的人肺的解剖位置。我们的LUNGMAP2中心将与 数据协调中心(DCC)、其他LUNGMAP2中心和人体组织采购 核心(HTPC)，使用最佳条件获取、注释、保存和存储人体组织 成像和组学分析。我们的LongMAP2项目将制作一份详细的结构表达图集 人类肺部的多个区域和壁龛。我们将开发和验证组织的新技术 清除、高分辨率图像的3D重建、多探针RNA和IF分析。我们会 为精确的区域生态位开发新的组织消化单细胞和单核RNA分析 来自患有罕见先天性肺病的婴儿的正常发育的人类肺组织。 我们将在一个联盟中工作，开发有用的生物信息学程序，对细胞-细胞、细胞基质进行建模 相互作用来定义信号和转录程序，建立和维持器官 结构和功能。与DCC和其他LongMAP2中心合作，我们的生物信息学 管道将在用户友好的门户网站中实现数据可视化和询问，以便与 LUNGMAP2联盟、DCC和整个研究界的成员。