Evidence map›Paper›PMID 38843840›Full record

ArticleCell systems2024

Stimulus-response signaling dynamics characterize macrophage polarization states.

Apeksha Singh, Supriya Sen, Michael Iter, Adewunmi Adelaja, Stefanie Luecke, Xiaolu Guo, Alexander Hoffmann

Abstract read
In one paragraph

Article in Cell systems, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Innate Immune Memory is Stimulus Specific.bioRxiv : the preprint server for biology · 2025
    Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Examining NF-κB genomic interactions by ChIP-seq and CUT&Tag.bioRxiv : the preprint server for biology · 2024
    Article
  15. Article
  16. Review
  17. Article
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

7 authors.

Apeksha SinghSignaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Supriya SenSignaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Michael IterSignaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Adewunmi AdelajaSignaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Stefanie LueckeSignaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Xiaolu GuoSignaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Alexander HoffmannSignaling Systems Laboratory, Department of Microbiology, Immunology, and Molecular Genetics, and Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: ahoffmann@ucla.edu.

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
Systems in Integrative BiologyT32GM008185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHOU, TOM · 1987 to 2022
$4.6M
Characterizing functional states of macrophages via their stimulus-responsesR01AI173214 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Alexander Hoffmann · 2023 to 2026
$2.8M
The NFkB System in Dendritic CellsR01AI127867 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HOFFMANN, ALEXANDER · 2018 to 2022
$2.2M
NFkB Signaling in MacrophagesR01AI127864 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HOFFMANN, ALEXANDER · 2017 to 2021
$1.9M
NIAID NIH HHS R01 AI127864NIAID NIH HHS R01 AI127867NIAID NIH HHS R01 AI173214NIGMS NIH HHS T32 GM008042NIGMS NIH HHS T32 GM008185
6 · The paper itself

Abstract

The functional state of cells is dependent on their microenvironmental context. Prior studies described how polarizing cytokines alter macrophage transcriptomes and epigenomes. Here, we characterized the functional responses of 6 differentially polarized macrophage populations by measuring the dynamics of transcription factor nuclear factor κB (NF-κB) in response to 8 stimuli. The resulting dataset of single-cell NF-κB trajectories was analyzed by three approaches: (1) machine learning on time-series data revealed losses of stimulus distinguishability with polarization, reflecting canalized effector functions. (2) Informative trajectory features driving stimulus distinguishability ("signaling codons") were identified and used for mapping a cell state landscape that could then locate macrophages conditioned by an unrelated condition. (3) Kinetic parameters, inferred using a mechanistic NF-κB network model, provided an alternative mapping of cell states and correctly predicted biochemical findings. Together, this work demonstrates that a single analyte's dynamic trajectories may distinguish the functional states of single cells and molecular network states underlying them. A record of this paper's transparent peer review process is included in the supplemental information.

Indexed as

MacrophagesNF-kappa BSignal TransductionAnimalsCell PolarityCytokinesHumansMachine LearningMacrophage ActivationMiceSingle-Cell AnalysisCytokinesNF-kappa Binflammationinnate immunitymachine learningmacrophagemath modelingmicroenvironmental contextNF-κB dynamicspolarizationstimulus-specific responsestrajectory data

Identifiers

PMID38843840
PMCPMC11226196

What OpenQuestion holds

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LicenceCC BY-NC
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.