Normal Aging Lung Cell Atlas (NALCA)

正常老化肺细胞图谱 (NALCA)

基本信息

批准号：
10275008
负责人：
NAFTALI KAMINSKI
金额：
$ 8.6万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-01-01 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10275008
关键词：
Acute Address Adult Age Aging Alveolar Alveolar Macrophages Atlases B-Lymphocytes Biological Biomedical Engineering Birth COVID-19 pandemic Cell Aging Cells Characteristics Chronic Obstructive Airway Disease Chronic lung disease Chronology Code Communities Computational Biology Computer Analysis Data Development Disease Disease susceptibility Elderly Endothelial Cells Environmental and Occupational Exposure Epidemiology Epigenetic Process Epithelial Cells Fibroblasts Gene Expression Profiling Generations Genetic Transcription Genomic Instability Genomics Goblet Cells Gonadal Steroid Hormones Human Immune response Immunohistochemistry In Situ Hybridization Incidence Individual Life Lung Lung diseases Lung infections Malignant Neoplasms Malignant neoplasm of lung Messenger RNA Methylation MicroRNAs Modeling Molecular Mus National Heart, Lung, and Blood Institute Nuclear Organ Outcome Parents Pathogenesis Play Predisposition Proteomics Pulmonary Hypertension Resources Respiratory System Respiratory Tract Infections Role Sampling Sex Differences Smooth Muscle Myocytes Structure Structure of parenchyma of lung Systems Biology T-Lymphocyte Time Tissue Engineering Tissue-Specific Gene Expression United States National Institutes of Health Untranslated RNA Validation Wild Type Mouse Woman Work aged base biological sex cell type detection of nutrient epigenomics exhaustion experience experimental study functional disability high throughput technology idiopathic pulmonary fibrosis intercellular communication laser capture microdissection macrophage men mitochondrial dysfunction monocyte mortality multidisciplinary multiple omics neutrophil normal aging novel proteostasis pulmonary function respiratory smooth muscle response sex sexual dimorphism single-cell RNA sequencing stem cells synergism telomere transcriptomics

项目摘要

PROJECT SUMMARY AND SUPPLEMENT TO U01 The overall objective of the ‘Normal Aging Lung Cell Atlas’ (NALCA), our response to RFA-HL-19-012 (Deciphering the Molecular Landscape of Lung Aging in Humans U01), is to generate a compendium of the dynamic cell specific changes in mRNA, microRNA, and epigenetic marks that happen during lung aging with a focus on single cells and the alveolar microenvironment. We plan to use this compendium to generate a dynamic temporal regulatory model of normal human lung aging. To address this objective, we have assembled a multidisciplinary group of experts in lung genomics, epigenomics, bioengineering, aging, alveolar development, systems and computational biology. The premise of this proposal lies in the availability of resources, including normal human lungs at different ages, aged wild-type and aging relevant genetically modified mice, unique expertise in high throughput technologies including single cell RNAseq, laser capture microdissection, methylation profiling, proteomics and tissue engineering, and proven track record in developmental of analytical approaches that dissect temporal regulatory networks. This objective also largely benefits from synergisms with other non-overlapping NIH-NHLBI and NIH-NIA projects headed by the coinvestigators on this proposal. We will address the objectives of this application by the following specific aims: Aim 1: To identify cell and microenvironment specific changes in coding and non-coding RNAs across human lung aging. Aim 2: To identify key time points in lung aging using detailed temporal analysis of mouse lung aging. Aim 3: To develop a comprehensive transcriptional dynamic regulatory multicellular model of lung aging. The completion of these specific aims will lead to the generation of the Normal Lung Aging Cell Atlas – a resource for the scientific community that will allow both better understanding of normal lung resident cell aging, as well as the role of aging related mechanisms in other chronic lung diseases.

项目摘要和 U01 的补充 “正常衰老肺细胞图谱”(NALCA) 的总体目标，我们对 RFA-HL-19-012 的回应（破译人类肺衰老的分子景观 U01），是为了生成一个纲要肺衰老过程中 mRNA、microRNA 和表观遗传标记的动态细胞特异性变化我们计划使用这个纲要来生成动态的单细胞和肺泡微环境。为了实现这一目标，我们建立了一个正常人类肺部衰老的时间调节模型。肺基因组学、表观基因组学、生物工程、衰老、肺泡发育等多学科专家组，该提案的前提在于资源的可用性，包括不同年龄的正常人肺，衰老的野生型和衰老相关的转基因小鼠，独特高通量技术方面的专业知识，包括单细胞 RNAseq、激光捕获显微切割、甲基化分析、蛋白质组学和组织工程，以及分析开发方面的良好记录剖析时间调控网络的方法也很大程度上受益于与时域调控网络的协同作用。由共同研究者领导的关于本提案的其他非重叠的 NIH-NHLBI 和 NIH-NIA 项目我们将进行。通过以下具体目标来解决本申请的目标：目标 1：识别细胞和人类肺部衰老过程中编码和非编码 RNA 的微环境特异性变化。使用小鼠肺衰老的详细时间分析来确定肺衰老的关键时间点目标 3：开发一个模型。肺衰老的综合转录动态调节多细胞模型的完成。具体目标将导致正常肺衰老细胞图谱的生成——这是科学界的资源社区将有助于更好地了解正常的肺常驻细胞衰老以及衰老的作用其他慢性肺部疾病的相关机制。