ArticlePLoS biology2013
Hybrid T-helper cells: stabilizing the moderate center in a polarized system.
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 24 papers.
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Who cites it
24 citing papers in PubMed.
- Emergent dynamics of cellular decision making in multi-node mutually repressive regulatory networks.Journal of the Royal Society, Interface · 2025Article
- Spatiotemporal Patterning Enabled by Gene Regulatory Networks.ACS omega · 2023Article
- Heterogeneity and clonality of kidney-infiltrating T cells in murine lupus nephritis.JCI insight · 2022Article
- Review
- Identification, visualization, statistical analysis and mathematical modeling of high-feedback loops in gene regulatory networks.BMC bioinformatics · 2021Article
- Multi-stability in cellular differentiation enabled by a network of three mutually repressing master regulators.Journal of the Royal Society, Interface · 2020Article
- Emergent Properties of the HNF4α-PPARγ Network May Drive Consequent Phenotypic Plasticity in NAFLD.Journal of clinical medicine · 2020Article
- Quantifying Cancer Epithelial-Mesenchymal Plasticity and its Association with Stemness and Immune Response.Journal of clinical medicine · 2019Review
- Variable cellular decision-making behavior in a constant synthetic network topology.BMC bioinformatics · 2019Article
- Towards control of cellular decision-making networks in the epithelial-to-mesenchymal transition.Physical biology · 2019Review
- An enriched network motif family regulates multistep cell fate transitions with restricted reversibility.PLoS computational biology · 2019Article
- Intermediate cell states in epithelial-to-mesenchymal transition.Physical biology · 2019Review
- Analysis of Single-Cell Gene Pair Coexpression Landscapes by Stochastic Kinetic Modeling Reveals Gene-Pair Interactions in Development.Frontiers in genetics · 2019Article
- Cell fate potentials and switching kinetics uncovered in a classic bistable genetic switch.Nature communications · 2018Article
- Making lineage decisions with biological noise: Lessons from the early mouse embryo.Wiley interdisciplinary reviews. Developmental biology · 2018Review
- Exploring intermediate cell states through the lens of single cells.Current opinion in systems biology · 2018Article
- The Human Cell Atlas.eLife · 2017Article
- The CD4+ T cell regulatory network mediates inflammatory responses during acute hyperinsulinemia: a simulation study.BMC systems biology · 2017Article
- Phenotypic Plasticity and Cell Fate Decisions in Cancer: Insights from Dynamical Systems Theory.Cancers · 2017Review
- Interrogating the topological robustness of gene regulatory circuits by randomization.PLoS computational biology · 2017Article
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Authors and funding
1 author.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polarization of cell phenotypes, a common strategy to achieve cell type diversity in metazoa, results from binary cell-fate decisions in the branching pedigree of development. Such "either-or" fate decisions are controlled by two opposing cell fate-determining transcription factors. Each of the two distinct "master regulators" promotes differentiation of its respective sister lineage. But they also suppress one other, leading to their mutually exclusive expression in the two ensuing lineages. Thus, promiscuous coexistence of the antagonist regulators in the same cell, the hallmark of the common "undecided" progenitor of two sister lineages, is considered unstable. This antagonism ensures robust polarization into two discretely distinct cell types. But now the immune system's T-helper (Th) cells and their two canonical subtypes, Th1 and Th2 cells, tell a different story, as revealed in three papers recently published in PLOS Biology. The intermediate state that co-expresses the two opposing master regulators of the Th1 and Th2 subtypes, T-bet and Gata3, is highly stable and is not necessarily an undecided precursor. Instead, the Th1/Th2 hybrid cell is a robust new type with properties of both Th1 and Th2 cells. These hybrid cells are functionally active and possess the benefit of moderation: self-limitation of effector T cell function to prevent excessive inflammation, a permanent risk in host defense that can cause tissue damage or autoimmunity. Gene regulatory network analysis suggests that stabilization of the intermediate center in a polarizing system can be achieved by minor tweaking of the architecture of the mutual suppression gene circuit, and thus is a design option readily available to evolution.
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