ArticleJournal of the Royal Society, Interface2020
Multi-stability in cellular differentiation enabled by a network of three mutually repressing master regulators.
Article in Journal of the Royal Society, Interface, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 55 citations in OpenAlex.
- UNified FramewOrk for reguLatory Dynamics (UNFOLD): Dissecting robustness, plasticity, evolvability and canalisation of biological function.PLoS computational biology · 2026Article
- Network hypermotifs in biological systems: structure, dynamics, and functional implications.NPJ systems biology and applications · 2026Review
- Article
- Emergent dynamics of cellular decision making in multi-node mutually repressive regulatory networks.Journal of the Royal Society, Interface · 2025Article
- Augmenting flexibility: mutual inhibition between inhibitory neurons expands functional diversity.iScience · 2025Article
- Low dimensionality of phenotypic space as an emergent property of coordinated teams in biological regulatory networks.iScience · 2025Article
- Operating principles of interconnected feedback loops driving cell fate transitions.NPJ systems biology and applications · 2025Article
- Multistability and predominant hybrid phenotypes in a four node mutually repressive network of Th1/Th2/Th17/Treg differentiation.NPJ systems biology and applications · 2024Article
- Network topology and interaction logic determine states it supports.NPJ systems biology and applications · 2024Review
- Assessing biological network dynamics: comparing numerical simulations with analytical decomposition of parameter space.NPJ systems biology and applications · 2023Article
- Article
- Universal structures for adaptation in biochemical reaction networks.Nature communications · 2023Article
- Spatiotemporal Patterning Enabled by Gene Regulatory Networks.ACS omega · 2023Article
- What Makes a Functional Gene Regulatory Network? A Circuit Motif Analysis.The journal of physical chemistry. B · 2022Article
- Article
- Article
- Dynamics of hepatocyte-cholangiocyte cell-fate decisions during liver development and regeneration.iScience · 2022Article
- Emergent dynamics of a three-node regulatory network explain phenotypic switching and heterogeneity: a case study of Th1/Th2/Th17 cell differentiation.Molecular biology of the cell · 2022Article
- A robust method for designing multistable systems by embedding bistable subsystems.NPJ systems biology and applications · 2022Article
- Article
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
No grant is acknowledged in the PubMed record.
Abstract
Identifying the design principles of complex regulatory networks driving cellular decision-making remains essential to decode embryonic development as well as enhance cellular reprogramming. A well-studied network motif involved in cellular decision-making is a toggle switch-a set of two opposing transcription factors A and B, each of which is a master regulator of a specific cell fate and can inhibit the activity of the other. A toggle switch can lead to two possible states-(high A, low B) and (low A, high B)-and drives the 'either-or' choice between these two cell fates for a common progenitor cell. However, the principles of coupled toggle switches remain unclear. Here, we investigate the dynamics of three master regulators A, B and C inhibiting each other, thus forming three-coupled toggle switches to form a toggle triad. Our simulations show that this toggle triad can lead to co-existence of cells into three differentiated 'single positive' phenotypes-(high A, low B, low C), (low A, high B, low C) and (low A, low B, high C). Moreover, the hybrid or 'double positive' phenotypes-(high A, high B, low C), (low A, high B, high C) and (high A, low B, high C)-can coexist together with 'single positive' phenotypes. Including self-activation loops on A, B and C can increase the frequency of 'double positive' states. Finally, we apply our results to understand cellular decision-making in terms of differentiation of naive CD4
Indexed as
Identifiers
What OpenQuestion holds
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.