ArticlePLoS computational biology2010
Modeling reveals bistability and low-pass filtering in the network module determining blood stem cell fate.
Article in PLoS computational biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Biophysical modeling reveals the transcriptional regulatory mechanism of Spo0A, the master regulator in starvingmSystems · 2025Article
- Unveiling the complexity of transcription factor networks in hematopoietic stem cells: implications for cell therapy and hematological malignancies.Frontiers in oncology · 2023Review
- Modularity in Biological Networks.Frontiers in genetics · 2021Review
- Maximization of information transmission influences selection of native phosphorelay architectures.PeerJ · 2021Article
- How Does the Regulatory Genome Work?Journal of computational biology : a journal of computational molecular cell biology · 2019Article
- Kinetic models of hematopoietic differentiation.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Review
- Assessing regulatory information in developmental gene regulatory networks.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- A quantitative proteomics approach identifies ETV6 and IKZF1 as new regulators of an ERG-driven transcriptional network.Nucleic acids research · 2016Article
- Determining Physical Mechanisms of Gene Expression Regulation from Single Cell Gene Expression Data.PLoS computational biology · 2016Article
- Article
- Transplantation of Macaca cynomolgus iPS-derived hematopoietic cells in NSG immunodeficient mice.Haematologica · 2015Article
- Article
- Transcriptional network control of normal and leukaemic haematopoiesis.Experimental cell research · 2014Review
- Transcriptional mechanisms of cell fate decisions revealed by single cell expression profiling.BioEssays : news and reviews in molecular, cellular and developmental biology · 2014Article
- Systems analysis of high-throughput data.Advances in experimental medicine and biology · 2014Review
- Dynamic analysis of gene expression and genome-wide transcription factor binding during lineage specification of multipotent progenitors.Cell stem cell · 2013Article
- GATA2 haploinsufficiency caused by mutations in a conserved intronic element leads to MonoMAC syndrome.Blood · 2013Article
- Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis.Nature cell biology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Combinatorial regulation of gene expression is ubiquitous in eukaryotes with multiple inputs converging on regulatory control elements. The dynamic properties of these elements determine the functionality of genetic networks regulating differentiation and development. Here we propose a method to quantitatively characterize the regulatory output of distant enhancers with a biophysical approach that recursively determines free energies of protein-protein and protein-DNA interactions from experimental analysis of transcriptional reporter libraries. We apply this method to model the Scl-Gata2-Fli1 triad-a network module important for cell fate specification of hematopoietic stem cells. We show that this triad module is inherently bistable with irreversible transitions in response to physiologically relevant signals such as Notch, Bmp4 and Gata1 and we use the model to predict the sensitivity of the network to mutations. We also show that the triad acts as a low-pass filter by switching between steady states only in response to signals that persist for longer than a minimum duration threshold. We have found that the auto-regulation loops connecting the slow-degrading Scl to Gata2 and Fli1 are crucial for this low-pass filtering property. Taken together our analysis not only reveals new insights into hematopoietic stem cell regulatory network functionality but also provides a novel and widely applicable strategy to incorporate experimental measurements into dynamical network models.
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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.