Stimulus-response signaling dynamics characterize macrophage polarization states.
Cell Syst
; 15(6): 563-577.e6, 2024 Jun 19.
Article
en En
| MEDLINE
| ID: mdl-38843840
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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
FN-kappa B
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Macrófagos
Límite:
Animals
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Humans
Idioma:
En
Revista:
Cell Syst
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos