Single Nucleus Multiomic Profiling Reveals Age-Dynamic Regulation of Host Genes Associated with SARS-CoV-2 Infection

Allen Wang; Joshua A Chiou; Olivier B Poirion; Justin Buchanan; Michael J Valdez; Jamie M Verheyden; Xiaomeng Hou; Minzhe Guo; Jacklyn M Newsome; Parul Kudtarkar; Dina A Faddah; Kai Zhang; Randee E Young; Justinn Barr; Ravi Misra; Heidie Huyck; Lisa Rogers; Cory Poole; Jeffery A Whitsett; Gloria Pryhuber; Yan Xu; Kyle J Gaulton; Sebastian Preissl; Xin Sun

demonstrate that many fewer children tested positive for SARS-CoV-2 infection, and 149 those who tested positive generally show less severe symptoms than adults or elderly 150 individuals (Bi et al., 2020; CDC, 2020) . This age divide coincides with the finding that 151 normal lung development in humans continues until the early 20s (Narayanan et al., 152 2012) . Therefore COVID-19 preferentially impacts fully mature lungs relative to 153 developing lungs. Widespread speculation has attempted to explain these age-154 associated differences, including immune senescence in the aging population. Defining 155 the mechanism underlying the apparent resistance of children to COVID-19 will inform 156 how we can transfer this resistance to adult and elderly populations. To profile cell type specific gene expression and accessible chromatin dynamics in 163 the human lung, we performed single nucleus RNA-seq (snRNA-seq) and single nucleus 164 ATAC-seq (snATAC-seq) of non-diseased human lung tissue from donors of three age 165 groups: ~30 week old gestational age (GA, prematurely born, 30wk GA ), ~3 year old (3yo), 166