Molecular anatomy of human alveolar development

人类肺泡发育的分子解剖学

• 批准号: 9066203
• 负责人: DAVID WARBURTON
• 金额: $ 81.1万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9066203
• 关键词: Adolescent; Adult; Alveolar; Alveolus; Anatomy; Area; Atlases; Biology; Blood Vessels; Blood capillaries; Boxing; Breathing; Bronchopulmonary Dysplasia; Cell Count; Cells; Chest; Child; Collaborations; Communities; Custom; Data; Development; Diagnostic radiologic examination; Distal; Dose; Drosophila genus; Ensure; Epithelial; Epithelial Cells; Event; Extracellular Matrix Proteins; Film; Fluorescent in Situ Hybridization; Four-dimensional; Future; Gene Expression; Goals; Health; Histology; Human; Image; Immunohistochemistry; In Situ Hybridization; Inferior; Investments; Knowledge; Length; Lobe; Lung; Lung diseases; Lymphatic; Magnetic Resonance Imaging; Maps; Mesenchymal; Microanatomy; Molecular; Molecular Genetics; Monkeys; Mus; Natural regeneration; Paraffin Embedding; Pattern; Phase; Plastic Embedding; Pregnancy; Prevention; Procedures; Process; Publishing; Radiation; Research; Resolution; Resources; Roentgen Rays; Scanning; Scientist; Selection Bias; Slice; Staging; Structure; Structure of parenchyma of lung; Surface; Techniques; Technology; Third Pregnancy Trimester; Time; Tissue Procurements; Tissues; Translating; Work; abstracting; capillary; combinatorial; data management; design; digital; digital imaging; human tissue; image processing; in utero; in vivo; innovation; lung development; lung maturation; microCT; novel; organ growth; postnatal; premature neonates; relating to nervous system; spatiotemporal; surfactant; time use

DESCRIPTION (provided by applicant): The following Goals are designed to achieve the overarching Strategic Goal to construct a rich multiscale atlas of human alveolar development and to readily share the resulting materials with other research centers in the UO1 and with the broad research community. Goal 1. Make a digital map of alveolar development over time in vivo and in tissue pieces using novel micro- CT (uCT), micro MRI (uMRI) and Phase contrast X-ray (PCX) technology validated in mice and then in human lung tissue. Goal 2. Make a digital map of spatiotemporal gene expression during alveolar development over time using newly modified high throughput multiplex ISH with novel "slice and dice", Vibra-SSIM confocal technology, in mouse and human lung tissue. Goal 3. Make a digital map of the fine structure of alveolar matrix during development in mouse and human tissue. Goal 4. Develop image-processing technology to meld digital multiscale images of alveolar structure with cell autonomous gene expression with extracellular matrix protein configuration into a readily navigable, annotated novel data resource for the scientific community. SOPs will be developed and process driven milestones will be set up to ensure deliverability and return on this significant scientific investment. Drs. Warburton, Shi and Driscoll are expert alveolar biologists while Drs. Fraser, Moats and Lansford are expert imaging scientists who are adept at recording, registering and assembling digital, multiscale combinatorial maps of organ development in Drosophila and Mouse and have invented many novel and highly innovative techniques to do so. Overall impact on human health: Human and mouse lung are fundamentally structurally different (reviewed in Warburton et al, 2010). Length of gestation, lobation, airway branch pattern, number of airway branches, proximo-distal airway epithelial differentiation and alveolar epithelial and capillary surface area as well as alveolar epithelial cell number differ in importan respects between mouse and human. Not least, alveolarization begins postnatally in mice, yet begins in utero in humans. We propose eventually to translate our novel concepts on alveolar development derived in mice rapidly to studies in vivo in humans. We hope that this fundamental knowledge will eventually be useful for the prevention and treatment of alveolar hypoplasia, such as occurs in bronchopulmonary dysplasia of the human premature neonate, as well as potentially to informing regeneration of alveolar tissue or amelioration or reversal of alveolar degeneration in older children, adolescents and adults with lung diseases. (End of Abstract)

描述（由申请人提供）：以下目标旨在实现总体战略目标，即构建一个丰富的多尺度人类肺泡发育图谱，并随时与UO 1的其他研究中心和广泛的研究社区分享所得材料。目标1.使用在小鼠中以及随后在人肺组织中验证的新型微CT（uCT）、微MRI（uMRI）和相位对比X射线（PCX）技术，制作体内和组织块中随时间推移的肺泡发育的数字图。目标2.在小鼠和人肺组织中，使用新修改的高通量多重ISH与新的“切片和骰子”，Vibra-SSIM共聚焦技术，制作肺泡发育期间随时间推移的时空基因表达的数字图。目标3.制作小鼠和人体组织发育过程中肺泡基质精细结构的数字地图。目标4.开发图像处理技术，将肺泡结构的数字多尺度图像与细胞自主基因表达和细胞外基质蛋白质结构融合成一个易于导航的，注释的新数据资源，供科学界使用。将制定SOP，并设置流程驱动的里程碑，以确保这一重大科学投资的可交付性和回报。Warburton博士、Shi博士和Drivel博士是肺泡生物学家专家，而Fraser博士、Moats博士和Lansford博士是成像科学家专家，擅长记录、记录和组装果蝇和小鼠器官发育的数字化、多尺度组合图，并发明了许多新颖和高度创新的技术。对人类健康的总体影响：人类和小鼠的肺在结构上存在根本性差异（综述见Warburton et al，2010）。小鼠和人的妊娠时间、分叶、气道分支模式、气道分支数量、近端-远端气道上皮分化、肺泡上皮和毛细血管表面积以及肺泡上皮细胞数量在重要方面存在差异。更重要的是，肺泡形成在小鼠出生后开始，而在人类子宫内开始。我们建议最终翻译我们的新概念，肺泡发育小鼠迅速在人体内的研究。我们希望这一基本知识最终将有助于预防和治疗肺泡发育不全，如发生在人类早产儿的支气管肺发育不良，以及潜在地告知肺泡组织的再生或改善或逆转患有肺部疾病的年龄较大的儿童，青少年和成人的肺泡变性。(End摘要）