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Although cytokine-dependent dynamics of nuclear factor κB (NF-κB) are known to encode information that regulates cell fate decisions, it is unclear whether single-cell responses are switch-like or encode more information about cytokine dose. Here, we measure the dynamic subcellular localization of NF-κB in response to a range of tumor necrosis factor (TNF) stimulation conditions to determine the prevailing mechanism of single-cell dose discrimination. Using an information theory formalism that accounts for signaling dynamics and non-responsive cell subpopulations, we find that the information transmission capacity of single cells exceeds that predicted from a switch-like response. Instead, we observe that NF-κB dynamics within single cells contain sufficient information to encode multiple, TNF-dependent cellular states, and have an activation threshold that varies across the population. By comparing single-cell responses to an internal, experimentally observed reference, we demonstrate that cells can grade responses to TNF across several orders of magnitude in concentration. This suggests that cells contain additional control points to fine-tune their cytokine responses beyond the decision to activate.
Pubmed ID: 29128333 RIS Download
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This polyclonal targets IgG
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View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
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View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsCell line KYM-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line U2OS is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis polyclonal targets GAPDH
View all literature mentionsThis monoclonal targets Lamin A/C
View all literature mentionsThis monoclonal targets beta-actin
View all literature mentionsThis monoclonal targets A20/TNFAIP3 (D13H3) Rabbit mAb
View all literature mentionsThis monoclonal targets NF-κB p65
View all literature mentionsThis unknown targets IgG (H+L)
View all literature mentionsThis monoclonal targets IkappaB-alpha
View all literature mentionsThis monoclonal targets TNFAIP3
View all literature mentionsThis monoclonal targets Genetic locus: RELA (human) mapping to 11q13.1; Rela (mouse) mapping to 19 A.
View all literature mentionsThis monoclonal targets beta-actin
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