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.