ArticleFrontiers in physiology2012
A stochastic model of epigenetic dynamics in somatic cell reprogramming.
Article in Frontiers in physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- The Role of Hydrogen Sulfide (HInternational journal of molecular sciences · 2023Pooled it
- The dynamics of chromatin states mediated by epigenetic modifications during somatic cell reprogramming.Frontiers in cell and developmental biology · 2023Review
- Organoid Cultures In Silico: Tools or Toys?Bioengineering (Basel, Switzerland) · 2022Review
- Epigenetic cell memory: The gene's inner chromatin modification circuit.PLoS computational biology · 2022Article
- Deep Hidden Physics Modeling of Cell Signaling Networks.Current genomics · 2021Article
- A mathematical model exhibiting the effect of DNA methylation on the stability boundary in cell-fate networks.Epigenetics · 2021Article
- Identification via Numerical Computation of Transcriptional Determinants of a Cell Phenotype Decision Making.Frontiers in genetics · 2019Article
- NetLand: quantitative modeling and visualization of Waddington's epigenetic landscape using probabilistic potential.Bioinformatics (Oxford, England) · 2017Article
- A predictive computational framework for direct reprogramming between human cell types.Nature genetics · 2016Article
- Efficient experimental design for uncertainty reduction in gene regulatory networks.BMC bioinformatics · 2015Article
- Modeling the epigenetic attractors landscape: toward a post-genomic mechanistic understanding of development.Frontiers in genetics · 2015Review
- Article
- Genome-scale modeling and human disease: an overview.Frontiers in physiology · 2014Article
- Single cell analysis reveals the stochastic phase of reprogramming to pluripotency is an ordered probabilistic process.PloS one · 2014Article
- End of inevitability: programming and reprogramming.Stem cell reviews and reports · 2013Article
- Reaction-contingency based bipartite Boolean modelling.BMC systems biology · 2013Article
- Recent development and biomedical applications of probabilistic Boolean networks.Cell communication and signaling : CCS · 2013Review
- Modeling to optimize terminal stem cell differentiation.Scientifica · 2013Review
- Qualitative modeling identifies IL-11 as a novel regulator in maintaining self-renewal in human pluripotent stem cells.Frontiers in physiology · 2013Article
- Relative stability of network states in Boolean network models of gene regulation in development.Bio SystemsArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Somatic cell reprogramming has dramatically changed stem cell research in recent years. The high pace of new findings in the field and an ever increasing amount of data from new high throughput techniques make it challenging to isolate core principles of the process. In order to analyze such mechanisms, we developed an abstract mechanistic model of a subset of the known regulatory processes during cell differentiation and production of induced pluripotent stem cells. This probabilistic Boolean network describes the interplay between gene expression, chromatin modifications, and DNA methylation. The model incorporates recent findings in epigenetics and partially reproduces experimentally observed reprogramming efficiencies and changes in methylation and chromatin remodeling. It enables us to investigate, how the temporal progression of the process is regulated. It also explicitly includes the transduction of factors using viral vectors and their silencing in reprogrammed cells, since this is still a standard procedure in somatic cell reprogramming. Based on the model we calculate an epigenetic landscape for probabilities of cell states. Simulation results show good reproduction of experimental observations during reprogramming, despite the simple structure of the model. An extensive analysis and introduced variations hint toward possible optimizations of the process that could push the technique closer to clinical applications. Faster changes in DNA methylation increase the speed of reprogramming at the expense of efficiency, while accelerated chromatin modifications moderately improve efficiency.
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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.