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| Status |
Public on Apr 23, 2021 |
| Title |
JAK inhibitors dampen activation of interferon-stimulated transcription of ACE2 isoforms in human airway epithelial cells (RNA-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
SARS-CoV-2 infection of human airway epithelium activates genetic programs leading to progressive hyperinflammation in COVID-19 patients. Here, we report on transcriptomes activated in primary airway cells by interferons and their suppression by Janus kinase (JAK) inhibitors. Deciphering the regulation of the angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, is paramount for understanding the cell tropism of SARS-CoV-2 infection. ChIP-seq for activating histone marks and Pol II loading identified candidate enhancer elements controlling the ACE2 locus, including the intronic dACE2 promoter. Employing RNA-seq, we demonstrate that interferons activate expression of dACE and, to a lesser extent, the genuine ACE2 gene. Interferon-induced gene expression was mitigated by the JAK inhibitors baricitinib and ruxolitinib used therapeutically in COVID-19 patients. Through integrating RNA-seq and ChIP-seq data we provide an in-depth understanding of genetic programs activated by interferons, and our study highlights JAK inhibitors as suitable tools to suppress these in bronchial cells.
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| |
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| Overall design |
RNA-seq was used to characterize chromatin structures and gene expression profiles in cytokine stimulation.
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| |
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| Contributor(s) |
Lee HK |
| Citation(s) |
33330857 |
| |
| Submission date |
Nov 17, 2020 |
| Last update date |
Apr 25, 2021 |
| Contact name |
Hye Kyung Lee |
| E-mail(s) |
hyekyung.lee@nih.gov
|
| Phone |
301-435-6635
|
| Organization name |
National Institutes of Health (NIH)
|
| Department |
National Institute of Diabetes and Digestive and Kidney (NIDDK)
|
| Lab |
Laboratory of Genetics and Physiology
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| Street address |
8 CENTER DR RM 107
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (37)
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| This SubSeries is part of SuperSeries: |
| GSE161665 |
JAK inhibitors dampen activation of interferon-stimulated transcription of ACE2 isoforms in human airway epithelial cells |
|
| Relations |
| BioProject |
PRJNA679047 |
| SRA |
SRP292952 |
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