ArticlePLoS biology2013
Stochastic cytokine expression induces mixed T helper cell States.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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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.
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Who cites it
41 citing papers in PubMed, 61 citations in OpenAlex.
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- Single-molecule imaging of transcription dynamics, RNA localization and fate in human T cells.The EMBO journal · 2025Article
- Independent and temporally separated dynamics for RORγt and Foxp3 during Th17 differentiation.Frontiers in immunology · 2025Article
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- Probing T-cell activation in nanoliter tumor co-cultures using membrane displacement trap arrays.Integrative biology : quantitative biosciences from nano to macro · 2024Article
- Single-cell analysis reveals TLR-induced macrophage heterogeneity and quorum sensing dictate population wide anti-inflammatory feedback in response to LPS.Frontiers in immunology · 2023Article
- The evolution of powerful yet perilous immune systems.Trends in immunology · 2022Review
- Dissecting the dynamic transcriptional landscape of early T helper cell differentiation into Th1, Th2, and Th1/2 hybrid cells.Frontiers in immunology · 2022Article
- RNA transport from transcription to localized translation: a single molecule perspective.RNA biology · 2021Review
- The Causes and Consequences of Spatial Organization of the Genome in Regulation of Gene Expression.Frontiers in immunology · 2021Review
- Differential expression profile of gluten-specific T cells identified by single-cell RNA-seq.PloS one · 2021Article
- Multi-stability in cellular differentiation enabled by a network of three mutually repressing master regulators.Journal of the Royal Society, Interface · 2020Article
- Quorum sensing via dynamic cytokine signaling comprehensively explains divergent patterns of effector choice among helper T cells.PLoS computational biology · 2020Article
- Modes of Communication between T Cells and Relevance for Immune Responses.International journal of molecular sciences · 2020Review
- Quantitative genetic analysis deciphers the impact of cis and trans regulation on cell-to-cell variability in protein expression levels.PLoS genetics · 2020Article
- A Darwinian and Physical Look at Stem Cell Biology Helps Understanding the Role of Stochasticity in Development.Frontiers in cell and developmental biology · 2020Article
- Single-Cell Transcriptome Profiling of Immune Cell Repertoire of the Atlantic Cod Which Naturally Lacks the Major Histocompatibility Class II System.Frontiers in immunology · 2020Article
- Challenges in measuring and understanding biological noise.Nature reviews. Genetics · 2019Review
- Single-cell Analysis of CAR-T Cell Activation Reveals A Mixed TGenomics, proteomics & bioinformatics · 2019Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
During eukaryotic development, the induction of a lineage-specific transcription factor typically drives differentiation of multipotent progenitor cells, while repressing that of alternative lineages. This process is often mediated by some extracellular signaling molecules, such as cytokines that can bind to cell surface receptors, leading to activation and/or repression of transcription factors. We explored the early differentiation of naive CD4 T helper (Th) cells into Th1 versus Th2 states by counting single transcripts and quantifying immunofluorescence in individual cells. Contrary to mutually exclusive expression of antagonistic transcription factors, we observed their ubiquitous co-expression in individual cells at high levels that are distinct from basal-level co-expression during lineage priming. We observed that cytokines are expressed only in a small subpopulation of cells, independent from the expression of transcription factors in these single cells. This cell-to-cell variation in the cytokine expression during the early phase of T helper cell differentiation is significantly larger than in the fully differentiated state. Upon inhibition of cytokine signaling, we observed the classic mutual exclusion of antagonistic transcription factors, thus revealing a weak intracellular network otherwise overruled by the strong signals that emanate from extracellular cytokines. These results suggest that during the early differentiation process CD4 T cells acquire a mixed Th1/Th2 state, instructed by extracellular cytokines. The interplay between extracellular and intracellular signaling components unveiled in Th1/Th2 differentiation may be a common strategy for mammalian cells to buffer against noisy cytokine expression.
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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.