Decoding the Cellular Niches Critical for Lung Maturation and Pathogenesis

解读对肺成熟和发病机制至关重要的细胞生态位

• 批准号: 10932692
• 负责人: Xin Sun
• 金额: $ 6.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-19 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10932692
• 关键词: ATAC-seq; Adopted; Aerosols; Alveolus; Antibodies; Architecture; Atlases; Bar Codes; Blood Vessels; Blood capillaries; Bronchopulmonary Dysplasia; Bypass; Cell Nucleus; Cells; Cellular biology; Child; Childhood; Chromatin; Clinical Investigator; Collaborations; Communities; Congenital diaphragmatic hernia; Coupled; Data; Databases; Developmental Biology; Disease; Dissociation; Endothelium; Environment; Epigenetic Process; Fibroblasts; Freezing; Gene Expression; Gene Expression Profile; Genes; Genomics; Goals; Human; Hyperplasia; Imaging technology; Immune; Immunology; In Situ Hybridization; Individual; Informatics; Interstitial Lung Diseases; Knowledge; Light; Lung; Lung diseases; Macrophage; Maps; Microscopy; Mission; Molecular; Neuroendocrine Cell; Organ; Pathogenesis; Patients; Pattern; Phase; Population; Positioning Attribute; Pulmonary Hypertension; RNA; Research; Resolution; Resources; Role; Sampling; Site; Smooth Muscle; Stains; Stress; Technology; Three-Dimensional Imaging; Tissues; United States National Institutes of Health; Work; cell type; combinatorial; differential expression; disease mechanisms study; empowerment; epigenome; epigenomics; human tissue; infancy; insight; lung maturation; meetings; nerve supply; neural; novel; pneumocyte; pulmonary function; regional difference; spatial integration; technology development; temporal measurement; transcriptome; transcriptome sequencing; transcriptomics; whole genome

PROJECT SUMMARY The human lung is vast organ with exquisite regional differences in the form of cellular niches best defined at single-cell resolution. Emerging evidence led to growing appreciation that the collective roles of these fine specializations are fundamental for lung function. Guided by the scientific premise that these niches are often sites of pathogenesis, we propose to map these niches in normal and disease tissues and directly compare them at the single-cell resolution. This goal is directly responsive to the mission of LungMap Phase 2 to “extend to more specific and rare cell types.” To achieve this goal, we have gathered an interdisciplinary team of established and rising, basic and clinical investigators with complementary strengths in developmental biology (Sun), cell biology and immunology (Prince, Sajti), technology development and informatics (Ren, Preissl, Wang and Xu). Together, we have a track record of studying the control of normal lung maturation, as well as mechanisms underlying a number of LungMap-highlighted diseases, including bronchopulmonary dysplasia, congenital diaphragmatic hernia, childhood interstitial lung disease, and pediatric pulmonary hypertension (PPH). We will use cutting-edge technologies such as single-nucleus ATACseq, single-cell and single-nucleus RNAseq, multiplex antibody and RNA in situ hybridization, and three-dimensional imaging. Using these, we will systematically define the exciting kaleidoscope of cell types in the human lung, with an emphasis on cellular niches that are central to pathogenesis.

项目摘要 人肺是巨大的器官，具有独家区域差异 最好在单细胞分辨率下定义细胞壁细分市场。新兴证据导致增长 感谢这些精细专业的集体角色是至关重要的 肺功能。在科学前提的指导下，这些利基通常是 发病机理，我们建议在正常组织和疾病组织中绘制这些壁ni，以及 直接以单细胞分辨率进行比较。这个目标直接响应 Lungmap第2阶段的任务“扩展到更具体和罕见的细胞类型”。 为了实现这一目标，我们聚集了一个跨学科的团队， 在发育方面具有完全优势的上升，基本和临床研究人员 生物学（Sun），细胞生物学和免疫学（Prince，Sajti），技术开发和 信息（Ren，Preissl，Wang和Xu）。在一起，我们有学习的记录 正常肺部成熟的控制以及许多机制 肺部高的疾病，包括支气管肺发育不良，先天性 diaphragmania疝气，儿童期间隙肺病和小儿肺 高血压（PPH）。我们将使用诸如单核等尖端技术 Atacseq，单细胞和单核RNASEQ，多种抗体和RNA原位 杂交和三维成像。使用这些，我们将系统地定义 人类肺中细胞类型的令人兴奋的万花筒，重点是细胞 发病机理中心的壁ni。