Decoding the Cellular Niches Critical for Lung Maturation and Pathogenesis

项目摘要： 人的肺是由一个分支网络的气道和血管，连接 数以百万计的肺泡进入气溶胶环境。编织成这个巨大的器官是精致的区域 在单细胞分辨率下最佳定义的细胞小生境形式的差异。新兴 越来越多的证据表明，这些专业人员之间的无缝合作 小生境是肺功能的基础。在科学前提的指导下，这些利基是 通常是发病部位，我们建议将其定位在正常和疾病肺的单个- 细胞分辨率这一目标直接响应了肺标测图第2阶段的使命，即“扩展到 更特殊和罕见的细胞类型。”以前研究的新见解使我们关注于 发病机制的关键小生境，包括气道分支点的肺/神经/免疫小生境， 肺泡的肺细胞/成纤维细胞/毛细血管/巨噬细胞龛，内皮细胞/平滑肌细胞 肺和支气管血管的肌肉龛。迈克尔巴尔德斯，申请人 补充，将提供额外的时间动态分析的数据，我们有 从父母的资助中产生。

Project Summary: The human lung is composed of a ramifying network of airways and blood vessels that connect millions of alveoli to the aerosol environment. Weaved into this vast organ are exquisite regional differences in the form of cellular niches best defined at single-cell resolution. Emerging evidence led to growing appreciation that seamless collaboration between these specialized niches are fundamental for lung function. Guided by the scientific premise that these niches are often sites of pathogenesis, we propose to map them in normal and disease lung 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.” Novel insights from previous studies have led us to focus on key niches of pathogenesis, including the lung/neural/immune niche at airway branch points, the pneumocyte/fibroblast/capillary/macrophage niche of the alveoli, the endothelium/smooth muscle niche of the pulmonary and bronchial vasculature. Michael Valdez, the applicant for this supplement, will be providing additional temporal dynamic analysis for the data we have generated from the parent grant.