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| Status |
Public on Dec 13, 2025 |
| Title |
Single-cell heterogeneity in interferon induction potential is heritable and governed by variation in cell state III |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Type I and III interferons (IFNs) are among the first lines of defense against viral infections, yet they are generally only produced by a tiny fraction of infected cells. Here, we show that variability in tonic cell signaling significantly influences cells’ ability to produce IFN upon stimulation with the synthetic double-stranded RNA, polyinosinic:polycytidylic acid (pIC). Using single-cell approaches, we found that members of the activator protein (AP)-1 transcription factor were implicated in IFNL1 expression predisposition. This guided us to investigate the role of the mitogen-activated protein kinase (MAPK) pathway, specifically the c-Jun N-terminal kinase (JNK), in IFNL1 production. We found that inhibition of JNK signaling severely altered the nature of the innate antiviral response upon pIC stimulation, independently of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Together, our study emphasizes the influence of intrinsic stochasticity in cell state on heterogeneity in IFN expression.
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| Overall design |
scRNAseq data of A549 cells either untreated or treated with 5 ng/mL pIC for 4, 8, 12, or 16 hours before being collected and processed for fixed scRNA sequencing.
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| Contributor(s) |
Thayer EA, Shipman G, Rivera-Cardona J, Mahajan T, Teo Q, Paez S, Lederer J, Chen J, Wu NC, Maslov S, Brooke CB |
| Citation missing |
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| Submission date |
Dec 09, 2025 |
| Last update date |
Dec 13, 2025 |
| Contact name |
Elizabeth Anne Thayer |
| E-mail(s) |
ethayer3@illinois.edu
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| Phone |
2179048965
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| Organization name |
University of Illinois at Urbana-Champaign
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| Department |
Microbiology
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| Lab |
Christopher Brooke
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| Street address |
407 S Goodwin Ave
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| City |
Urbana |
| State/province |
IL |
| ZIP/Postal code |
61801 |
| Country |
USA |
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| Platforms (1) |
| GPL34284 |
Illumina NovaSeq X Plus (Homo sapiens) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA1378218 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE313068_aggr_timepoints.csv.gz |
251 b |
(ftp)(http) |
CSV |
| GSE313068_barcodes_umap_probabilities_info.csv.gz |
3.7 Mb |
(ftp)(http) |
CSV |
| GSE313068_et02b04_feature_README.txt |
640 b |
(ftp)(http) |
TXT |
| GSE313068_et02b04_filtered_feature_bc_matrix.h5 |
414.2 Mb |
(ftp)(http) |
H5 |
| GSE313068_pool1_input.csv.gz |
331 b |
(ftp)(http) |
CSV |
| GSE313068_pool2_input.csv.gz |
332 b |
(ftp)(http) |
CSV |
| GSE313068_pool3_input.csv.gz |
339 b |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
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