Evidence map›Paper›PMID 26488364›Full record

ArticleeLife2015

Digital signaling decouples activation probability and population heterogeneity.

Ryan A Kellogg, Chengzhe Tian, Tomasz Lipniacki, Stephen R Quake, Savaş Tay

Open access · goldAbstract read
In one paragraph

Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
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

54 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
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  10. Probing T-cell activation in nanoliter tumor co-cultures using membrane displacement trap arrays.Integrative biology : quantitative biosciences from nano to macro · 2024
    Article
  11. Review
  12. Article
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  14. Droplets microfluidics platform-A tool for single cell research.Frontiers in bioengineering and biotechnology · 2023
    Review
  15. Article
  16. Article
  17. Mitochondrial signal transduction.Cell metabolism · 2022
    Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 4 institutions in 4 countries.

Ryan A KelloggDepartment of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, Basel, Switzerland.ORCID http://orcid.org/0000-0002-5591-9466
Chengzhe TianNiels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-2269-1979
Tomasz LipniackiInstitute of Fundamental Technological Research, Polish Academy of Sciences, Warsaw, Poland.
Stephen R QuakeDepartment of Bioengineering, Howard Hughes Medical Institute, Stanford University, Stanford, United States.
Savaş TayDepartment of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, Basel, Switzerland.
Board of the Swiss Federal Institutes of Technology · CHHoward Hughes Medical Institute · USInstitute of Fundamental Technological Research · PLUniversity of Copenhagen · DK

Funding

ULTRASTRUCTURE AND CYTOMORPHOLOGY COREP30DK042086 · NIDDK · UNIVERSITY OF CHICAGO · PI ABADIE, VALERIE · 1990 to 2025
$29.8M
6 · The paper itself

Abstract

Digital signaling enhances robustness of cellular decisions in noisy environments, but it is unclear how digital systems transmit temporal information about a stimulus. To understand how temporal input information is encoded and decoded by the NF-κB system, we studied transcription factor dynamics and gene regulation under dose- and duration-modulated inflammatory inputs. Mathematical modeling predicted and microfluidic single-cell experiments confirmed that integral of the stimulus (or area, concentration × duration) controls the fraction of cells that activate NF-κB in the population. However, stimulus temporal profile determined NF-κB dynamics, cell-to-cell variability, and gene expression phenotype. A sustained, weak stimulation lead to heterogeneous activation and delayed timing that is transmitted to gene expression. In contrast, a transient, strong stimulus with the same area caused rapid and uniform dynamics. These results show that digital NF-κB signaling enables multidimensional control of cellular phenotype via input profile, allowing parallel and independent control of single-cell activation probability and population heterogeneity.

Indexed as

Gene Expression RegulationSignal TransductionAnimalsCell LineFibroblastsMiceMicrofluidicsModels, TheoreticalNF-kappa BSingle-Cell AnalysisTime FactorsNF-kappa Bcell-to-cell heterogeneitycomputational biologydigital signalingimmunologyinnate immunitymousesignaling dynamicssingle-cell analysissystems biology

Identifiers

PMID26488364
PMCPMC4608393
OpenAlexW2175622107

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.