TY - JOUR T1 - Single Nucleus Multiomic Profiling Reveals Age-Dynamic Regulation of Host Genes Associated with SARS-CoV-2 Infection JF - bioRxiv DO - 10.1101/2020.04.12.037580 SP - 2020.04.12.037580 AU - Allen Wang AU - Joshua Chiou AU - Olivier B Poirion AU - Justin Buchanan AU - Michael J Valdez AU - Jamie M Verheyden AU - Xiaomeng Hou AU - Minzhe Guo AU - Jacklyn M Newsome AU - Parul Kudtarkar AU - Dina A Faddah AU - Kai Zhang AU - Randee E Young AU - Justinn Barr AU - Ravi Misra AU - Heidie Huyck AU - Lisa Rogers AU - Cory Poole AU - Jeffery A. Whitsett AU - Gloria Pryhuber AU - Yan Xu AU - Kyle J Gaulton AU - Sebastian Preissl AU - Xin Sun AU - NHLBI LungMap Consortium Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/14/2020.04.12.037580.abstract N2 - Respiratory failure is the leading cause of COVID-19 death and disproportionately impacts adults more than children. Here, we present a large-scale snATAC-seq dataset (90,980 nuclei) of the human lung, generated in parallel with snRNA-seq (46,500 nuclei), from healthy donors of ~30 weeks, ~3 years and ~30 years of age. Focusing on genes implicated in SARS-CoV-2 cell entry, we observed an increase in the proportion of alveolar epithelial cells expressing ACE2 and TMPRSS2 in adult compared to young lungs. Consistent with expression dynamics, 10 chromatin peaks linked to TMPRSS2 exhibited significantly increased activity with age and harbored IRF and STAT binding sites. Furthermore, we identified 14 common sequence variants in age-increasing peaks with predicted regulatory function, including several associated with respiratory traits and TMPRSS2 expression. Our findings reveal a plausible contributor to why children are more resistant to COVID-19 and provide an epigenomic basis for transferring this resistance to older populations.Competing Interest StatementKJG does consulting for Genentech, DAF is an employee and holds stock in Vertex Pharmaceuticals; no other relationships or activities that could appear to have influenced this work ER -