Evidence map›Paper›PMID 42462718›Full record

ArticleCell systems2026

Single-cell heterogeneity in interferon induction potential is heritable and governed by variation in cell state.

Elizabeth A Thayer, Gabriela Shipman, Joel Rivera-Cardona, Tarun Mahajan, Qi Wen Teo, J Sebastian Paez, Joseph Lederer, Jie Chen, Nicholas C Wu, Sergei Maslov and 1 more

Abstract read
In one paragraph

Article in Cell systems, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Elizabeth A ThayerDepartment of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Gabriela ShipmanDepartment of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Joel Rivera-CardonaDepartment of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Tarun MahajanDepartment of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Qi Wen TeoCarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA; Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA.
J Sebastian PaezTalus Bioscience, Seattle, WA, USA.
Joseph LedererCarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Jie ChenDepartment of Cell and Developmental Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA; Department of Biomedical and Translational Sciences, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA; Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Nicholas C WuCarl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA; Department of Biochemistry, University of Illinois Urbana-Champaign, Urbana, IL, USA; Department of Biomedical and Translational Sciences, Carle Illinois College of Medicine, University of Illinois Urbana-Champaign, Urbana, IL, USA; Center for Biophysics and Quantitative Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Sergei MaslovDepartment of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA; Center for Artificial Intelligence and Modeling, University of Illinois Urbana-Champaign, Urbana, IL, USA; Department of Physics, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Christopher B BrookeDepartment of Microbiology, University of Illinois Urbana-Champaign, Urbana, IL, USA; Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA. Electronic address: cbrooke@illinois.edu.

Funding

Phospholipase D signalingR01GM089771 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI CHEN, JIE · 2011 to 2025
$3.9M
Biophysical constraints of influenza neuraminidase evolutionR01AI165475 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI WU, NICHOLAS C. · 2022 to 2025
$2.0M
The effects of influenza virus genomic heterogeneity on replication dynamics and the host responseR01AI139246 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI BROOKE, CHRISTOPHER BYRON · 2018 to 2022
$1.9M
Dissecting the viral and host constraints that govern influenza virus antigenic evolutionR01AI179910 · NIAID · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Christopher Byron Brooke · 2024 to 2026
$1.5M
NIAID NIH HHS R01 AI139246NIAID NIH HHS R01 AI165475NIAID NIH HHS R01 AI179910NIGMS NIH HHS R01 GM089771
6 · The paper itself

Abstract

Type I and III interferons (IFNs) are among the first lines of defense against viral infection, yet they are generally only produced by a tiny fraction of infected cells. Here, we show that cellular heterogeneity in IFN-induction potential upon treatment with immunostimulatory RNA is not due to variability in sensing of stimuli but instead is shaped by heterogeneity in tonic cell signaling state. Using complementary single-cell approaches, we found that baseline variation in the expression of c-Jun N-terminal kinase (JNK) and activator protein (AP)-1 transcription factor families correlated with IFNL1 expression predisposition. We further show that drug-based inhibition of JNK signaling virtually eliminates the innate antiviral response to immunostimulatory RNA. Finally, we show that single-cell heterogeneity in IFN-induction potential is heritable and stably maintained over numerous generations. Together, our study emphasizes the influence of intrinsic variability in cell state on innate immune regulation and IFN-induction heterogeneity.

Identifiers

PMID42462718
PMCPMC13431654

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.