A single-cell chromatin accessibility map of pulmonary alveologenesis in humans and mice

Regulation of lung responses to air breathing and continued alveolar development shape ex-utero and adult respiratory health.  Applying single-cell transposome hypersensitive site sequencing (scTHS-seq) to human and mouse lung, we assembled a regulatory atlas of postnatal lung development and analyzed over 80,000 single-cells.  From day of life 1, we characterized cell types and cell-cell interactions driving alveoli generation.  We elucidated key transcription factor-gene accessibility modules (TF-GAM) guiding alveolar epithelial cell differentiation and epithelial-mesenchymal interactions involved in alveolar septation and mechanotransduction.  Incorporating GWAS causal variants, we identified lung pathogenic risk units enriched in specific cell types.  Our regulatory map and analysis model provide an effective resource to investigate age-dependent and species-specific control of critical developmental processes.  Furthermore, this resource complements single-cell atlas efforts to advance our understanding of lung health and disease across the human lifespan. Single DAPI+ nuclei (according to Samples list) were isolated from 4 separate postmortem human and 4 mouse distal lung parenchymal samples and processed for single-cell transposome hypersensitive site sequencing (scTHS-seq). ------------------- Submitter declares that the raw data will be submitted to dbGaP (https://www.ncbi.nlm.nih.gov/gap) because of patient privacy concerns.