ArticleeLife2017
Engineering of a synthetic quadrastable gene network to approach Waddington landscape and cell fate determination.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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.
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Who cites it
35 citing papers in PubMed.
- Oscillatory co-expression of HES1 and HES5 enables a hybrid state in a cross-repressive transcription factor regulatory motif.Development (Cambridge, England) · 2026Article
- Design principles of gene circuits for longevity.Trends in cell biology · 2025Review
- Engineering development: From the repressilator and toggle switch to synthetic developmental biology.Developmental biology · 2025Review
- Modeling combinatorial regulation from single-cell multi-omics provides regulatory units underpinning cell type landscape using cRegulon.Genome biology · 2025Article
- Modeling ncRNA-Mediated Circuits in Cell Fate Decision: From Systems Biology to Synthetic Biology.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Multistability and predominant hybrid phenotypes in a four node mutually repressive network of Th1/Th2/Th17/Treg differentiation.NPJ systems biology and applications · 2024Article
- Enhanced cellular longevity arising from environmental fluctuations.Cell systems · 2024Article
- Modularized Design and Construction of Tunable Microbial Consortia with Flexible Topologies.ACS synthetic biology · 2024Article
- Article
- Engineering longevity-design of a synthetic gene oscillator to slow cellular aging.Science (New York, N.Y.) · 2023Article
- Origin, heterogeneity, and interconversion of noncanonical bistable switches from the positive feedback loops under dual signaling.iScience · 2023Article
- Multiple Gene Expression in Cell-Free Protein Synthesis Systems for Reconstructing Bacteriophages and Metabolic Pathways.Microorganisms · 2022Review
- A Predictive Reaction-diffusion Based Model ofIEEE control systems letters · 2021Article
- An in vitro model of tumor heterogeneity resolves genetic, epigenetic, and stochastic sources of cell state variability.PLoS biology · 2021Article
- A Dimension Reduction Approach for Energy Landscape: Identifying Intermediate States in Metabolism-EMT Network.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Memorizing environmental signals through feedback and feedforward loops.Current opinion in cell biology · 2021Review
- Trajectory-based energy landscapes of gene regulatory networks.Biophysical journal · 2021Article
- Winner-takes-all resource competition redirects cascading cell fate transitions.Nature communications · 2021Article
- A programmable fate decision landscape underlies single-cell aging in yeast.Science (New York, N.Y.) · 2020Article
- Topology-dependent interference of synthetic gene circuit function by growth feedback.Nature chemical biology · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
The process of cell fate determination has been depicted intuitively as cells travelling and resting on a rugged landscape, which has been probed by various theoretical studies. However, few studies have experimentally demonstrated how underlying gene regulatory networks shape the landscape and hence orchestrate cellular decision-making in the presence of both signal and noise. Here we tested different topologies and verified a synthetic gene circuit with mutual inhibition and auto-activations to be quadrastable, which enables direct study of quadruple cell fate determination on an engineered landscape. We show that cells indeed gravitate towards local minima and signal inductions dictate cell fates through modulating the shape of the multistable landscape. Experiments, guided by model predictions, reveal that sequential inductions generate distinct cell fates by changing landscape in sequence and hence navigating cells to different final states. This work provides a synthetic biology framework to approach cell fate determination and suggests a landscape-based explanation of fixed induction sequences for targeted differentiation.
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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.