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| Status |
Public on Nov 23, 2020 |
| Title |
Single Nucleus ATAC-Seq Multiomic Profiling Reveals Age-Dynamic Regulation of Host Genes Associated with SARS-CoV-2 Infection [scATAC-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
snATAC-seq of human non-diseased lungs from donors of three age groups: ~30 week old gestational age (GA, prematurely born, 30wkGA), ~3 year old (3yo), and ~30 year old (30yo). Three lungs were sampled for each age group, with both males and females represented. Of the 9 donors, 5 were Caucasian, 1 was African American and 3 were of unknown ancestry. For all samples, flash frozen biopsies from equivalent small airway regions of the lung were used. Nuclei were isolated from individual biopsies and split into two pools, one for snRNA-seq and one for snATAC-seq. We generated technical replicates for one of the 3yo donors (D032). Donor lung samples were provided through the federal United Network of Organ Sharing via National Disease Research Interchange (NDRI) and International Institute for Advancement of Medicine (IIAM) and entered into the NHLBI LungMAP Biorepository for Investigations of Diseases of the Lung (BRINDL) at the University of Rochester Medical Center overseen by the IRB as RSRB00047606, as previously described (Ardini-Poleske et al., 2017; Bandyopadhyay et al., 2018). Portions (0.25-1.0 cm3) of small airway region of right middle lobe (RML) lung tissue were frozen in cryovials over liquid nitrogen and placed at −80°C for storage.
The raw sequencing data is available through dbGaP (controlled access) due to patient privacy concerns. https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001961.v1.p1
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| Contributor(s) |
Wang A, Chiou J, Poirion OB, Buchanan J, Valdez MJ, Verheyden JM, Hou X, Guo M, Newsome JM, Kudtarkar P, Faddah DA, Zhang K, Young RE, Barr J, Misra R, Huyck H, Rogers L, Poole C, Whitsett JA, Pryhuber G, Xu Y, Gaulton KJ, Preissl S, Sun X |
| Citation(s) |
33164753 |
| Submission date |
Nov 12, 2020 |
| Last update date |
Oct 18, 2022 |
| Contact name |
LungMAPP DCC |
| E-mail(s) |
lungmap2dcc@gmail.com
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| Organization name |
LungMAP DCC
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| Street address |
3333 Burnet Ave
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| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (11)
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| This SubSeries is part of SuperSeries: |
| GSE161383 |
Single Nucleus Multiomic Profiling Reveals Age-Dynamic Regulation of Host Genes Associated with SARS-CoV-2 Infection |
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| Relations |
| BioProject |
PRJNA677987 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE161381_RAW.tar |
1.5 Gb |
(http)(custom) |
TAR (of MTX, TSV) |
| GSE161381_lung_snATAC.UMAP.cluster_labels.txt.gz |
2.3 Mb |
(ftp)(http) |
TXT |
| Processed data provided as supplementary file |
| Raw data not provided for this record |
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