ArticleProceedings of the National Academy of Sciences of the United States of America2014
Stem cell differentiation as a many-body problem.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- Inferring stochastic dynamics by biophysical Neural ODE using single-cell transcriptomics.Nature communications · 2026Article
- General relationship of local topologies, global dynamics, and bifurcation in cellular networks.NPJ systems biology and applications · 2024Article
- Energy Landscape Reveals the Underlying Mechanism of Cancer-Adipose Conversion in Gene Network Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- Theoretical and computational tools to model multistable gene regulatory networks.Reports on progress in physics. Physical Society (Great Britain) · 2023Review
- Human Stem Cells for Ophthalmology: Recent Advances in Diagnostic Image Analysis and Computational Modelling.Current stem cell reports · 2023Review
- Quantitative landscapes reveal trajectories of cell-state transitions associated with drug resistance in melanoma.iScience · 2022Article
- Inferring structural and dynamical properties of gene networks from data with deep learning.NAR genomics and bioinformatics · 2022Article
- Perspectives on the landscape and flux theory for describing emergent behaviors of the biological systems.Journal of biological physics · 2022Review
- Landscape and kinetic path quantify critical transitions in epithelial-mesenchymal transition.Biophysical journal · 2021Article
- A Dimension Reduction Approach for Energy Landscape: Identifying Intermediate States in Metabolism-EMT Network.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Quantifying the Landscape of Decision Making From Spiking Neural Networks.Frontiers in computational neuroscience · 2021Article
- Conformational state switching and pathways of chromosome dynamics in cell cycle.Applied physics reviews · 2020Article
- Quantifying the Landscape and Transition Paths for Proliferation-Quiescence Fate Decisions.Journal of clinical medicine · 2020Article
- Decoding the mechanisms underlying cell-fate decision-making during stem cell differentiation by random circuit perturbation.Journal of the Royal Society, Interface · 2020Article
- Quantifying epigenetic stability with minimum action paths.Physical review. E · 2020Article
- Modeling binary and graded cone cell fate patterning in the mouse retina.PLoS computational biology · 2020Article
- Adaptive Landscape Shaped by Core Endogenous Network Coordinates Complex Early Progenitor Fate Commitments in Embryonic Pancreas.Scientific reports · 2020Article
- Automatic error control during forward flux sampling of rare events in master equation models.The Journal of chemical physics · 2020Article
- Quantifying the Stability of Coupled Genetic and Epigenetic Switches With Variational Methods.Frontiers in genetics · 2020Article
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2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stem cell differentiation has been viewed as coming from transitions between attractors on an epigenetic landscape that governs the dynamics of a regulatory network involving many genes. Rigorous definition of such a landscape is made possible by the realization that gene regulation is stochastic, owing to the small copy number of the transcription factors that regulate gene expression and because of the single-molecule nature of the gene itself. We develop an approximation that allows the quantitative construction of the epigenetic landscape for large realistic model networks. Applying this approach to the network for embryonic stem cell development explains many experimental observations, including the heterogeneous distribution of the transcription factor Nanog and its role in safeguarding the stem cell pluripotency, which can be understood by finding stable steady-state attractors and the most probable transition paths between those attractors. We also demonstrate that the switching rate between attractors can be significantly influenced by the gene expression noise arising from the fluctuations of DNA occupancy when binding to a specific DNA site is slow.
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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.