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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要人类的肺是一个巨大的器官，其形式存在着微妙的区域差异细胞生态位最好在单细胞分辨率下定义。新出现的证据导致了不断增长。认识到这些精细专业的集体作用对于以这些生态位通常是肺功能的科学前提为指导。发病机制，我们建议绘制正常和疾病组织中的这些生态位，直接在单细胞分辨率下比较它们，这个目标直接响应于 LungMap 第二阶段的使命是“扩展到更具体和稀有的细胞类型”。为了实现这一目标，我们聚集了一支由知名人士和专家组成的跨学科团队新兴的基础和临床研究人员在发展方面具有互补优势生物学（Sun）、细胞生物学和免疫学（Prince、Sajti）、技术开发和信息学（Ren、Preissl、Wang 和 Xu）一起，我们有研究记录。正常肺成熟的控制，以及许多潜在的机制 LungMap 突出显示的疾病，包括支气管肺发育不良、先天性膈疝、儿童间质性肺疾病和小儿肺病我们将使用单核等尖端技术。 ATACseq、单细胞和单核 RNAseq、多重抗体和 RNA 原位利用这些，我们将系统地定义杂交和三维成像。人肺细胞类型的令人兴奋的万花筒，重点是细胞是发病机制核心的生态位。