ArticleScience signaling2013
Cell-to-cell variability analysis dissects the plasticity of signaling of common γ chain cytokines in T cells.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
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- NF-kB in Signaling Patterns and Its Temporal Dynamics Encode/Decode Human Diseases.Life (Basel, Switzerland) · 2022Review
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- Modeling cell-specific dynamics and regulation of the common gamma chain cytokines.Cell reports · 2021Article
- Competing endogenous RNA crosstalk at system level.PLoS computational biology · 2019Article
- Quantifying the Dynamics of Hematopoiesis by In Vivo IdU Pulse-Chase, Mass Cytometry, and Mathematical Modeling.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2019Article
- Critical slowing down in biochemical networks with feedback.Physical review. E · 2019Article
- Constitutive Activation of the B Cell Receptor Underlies Dysfunctional Signaling in Chronic Lymphocytic Leukemia.Cell reports · 2019Article
- Mitochondrial origins of fractional control in regulated cell death.Nature communications · 2019Article
- A Two-Pulse Cellular Stimulation Test Elucidates Variability and Mechanisms in Signaling Pathways.Biophysical journal · 2019Article
- Universality of biochemical feedback and its application to immune cells.Physical review. E · 2019Article
- Modeling of cytometry data in logarithmic space: When is a bimodal distribution not bimodal?Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2018Article
- Nongenetic origins of cell-to-cell variability in B lymphocyte proliferation.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Mathematical modeling identifies Lck as a potential mediator for PD-1 induced inhibition of early TCR signaling.PloS one · 2018Article
- Review
- EGFR and PDGFRA co-expression and heterodimerization in glioblastoma tumor sphere lines.Scientific reports · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Natural variability in the abundance of signaling regulators can lead to divergence in cell fate, even within genetically identical cells that share a common differentiation state. We introduce cell-to-cell variability analysis (CCVA), an experimental and computational methodology that quantifies the correlation between variability in signaling regulator abundance and variation in the sensitivity of cells to stimuli. With CCVA, we investigated the unexpected effects of the interleukin 2 (IL-2) receptor α chain (IL-2Rα) on the sensitivity of primary mouse T lymphocytes to cytokines that signal through receptors that have the common γ chain (γ(c)). Our work showed that increased IL-2Rα abundance decreased the concentration of IL-2 required for a half-maximal activation (EC(50)) of the downstream effector signal transducer and activator of transcription 5 (STAT5), but reduced the responsiveness to IL-7 or IL-15, without affecting the EC(50) values of other γ(c) cytokines. To investigate the mechanism of the effect of IL-2Rα on γ(c) cytokine signaling, we introduced a Bayesian-inference computational framework that models the formation of receptor signaling complexes with data from previous biophysical measurements. With this framework, we found that a model in which IL-2Rα drives γ(c) depletion through the assembly of functional IL-2R complexes was consistent with both the CCVA data and experimental measurements. The combination of CCVA and computational modeling produced quantitative understanding of the crosstalk between γ(c) cytokine receptor signaling in T lymphocytes.
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Registered trials
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.