Single Nucleus Multiomic Profiling Reveals Age-Dynamic Regulation of Host Genes Associated with SARS-CoV-2 Infection
Wang, A.; Chiou, J. A.; Poirion, O. B.; Buchanan, J.; Valdez, M. J.; Verheyden, J. M.; Hou, X.; Guo, M.; Newsome, J. M.; Kudtarkar, P.; Faddah, D. A.; Zhang, K.; Young, R. E.; Barr, J.; Misra, R.; Huyck, H.; Rogers, L.; Poole, C.; Whitsett, J. A.; Pryhuber, G.; Xu, Y.; Gaulton, K. J.; Preissl, S.; Sun, X.; NHLBI LungMap Consortium,
Show abstract
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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Lung lineage transcription factor NKX2-1 epigenetically resolves opposing cell fates in vivo 95%
- Context-aware single-cell multiome approach identified cell-type specific lung cancer susceptibility genes 95%
- Type 2 and interferon inflammation strongly regulate SARS-CoV-2 related gene expression in the airway epithelium 94%
Similar papers in this journal
- Comprehensive characterization of the transcriptional response to COVID-19 in multiple organs reveals shared signatures across tissues 96%
- Injury-induced pulmonary tuft cells are heterogenous, arise independent of key Type 2 cytokines, and are dispensable for dysplastic repair 94%
- ACE2 is the critical in vivo receptor for SARS-CoV-2 in a novel COVID-19 mouse model with TNF- and IFNγ-driven immunopathology 94%
Similar papers in this journal
- A single-cell RNA expression map of human coronavirus entry factors 95%
- ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation. 94%
- ΔNp63 drives dysplastic alveolar remodeling and restricts epithelial plasticity upon severe lung injury 94%
Similar papers in this journal
- Image-based spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis 94%
- Genetics and Environment Distinctively Shape the Human Immune Cell Epigenome 94%
- Population-level variation of enhancer expression identifies novel disease mechanisms in the human brain 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.