ArticleBMC systems biology2014
Mathematical modeling of GATA-switching for regulating the differentiation of hematopoietic stem cell.
Article in BMC systems biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 36 citations in OpenAlex.
- Human Stem Cells for Ophthalmology: Recent Advances in Diagnostic Image Analysis and Computational Modelling.Current stem cell reports · 2023Review
- A robust method for designing multistable systems by embedding bistable subsystems.NPJ systems biology and applications · 2022Article
- Article
- Intracellular Energy Variability Modulates Cellular Decision-Making Capacity.Scientific reports · 2019Article
- Kinetic models of hematopoietic differentiation.Wiley interdisciplinary reviews. Systems biology and medicine · 2019Review
- Computational Analysis of Altering Cell Fate.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Stochastic multistationarity in a model of the hematopoietic stem cell differentiation network.Proceedings of the ... IEEE Conference on Decision & Control. IEEE Conference on Decision & Control · 2018Article
- Reverse-engineering of gene networks for regulating early blood development from single-cell measurements.BMC medical genomics · 2017Article
- The transcription factor GATA1 regulates NBEAL2 expression through a long-distance enhancer.Haematologica · 2017Article
- Mathematical Models for Immunology: Current State of the Art and Future Research Directions.Bulletin of mathematical biology · 2016Review
- E2F and GATA switches turn off WD repeat domain 77 expression in differentiating cells.The Biochemical journal · 2016Article
- Generalized logical model based on network topology to capture the dynamical trends of cellular signaling pathways.BMC systems biology · 2016Article
- Power-Law Modeling of Cancer Cell Fates Driven by Signaling Data to Reveal Drug Effects.PloS one · 2016Article
- Normal vs. Malignant hematopoiesis: the complexity of acute leukemia through systems biology.Frontiers in genetics · 2015Article
- A continuous optimization approach for inferring parameters in mathematical models of regulatory networks.BMC bioinformatics · 2014Article
- Approximate Bayesian computation schemes for parameter inference of discrete stochastic models using simulated likelihood density.BMC bioinformatics · 2014Article
- Reprogramming multistable monotone systems with application to cell fate control.IEEE transactions on network science and engineeringArticle
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHematopoiesis is a highly orchestrated developmental process that comprises various developmental stages of the hematopoietic stem cells (HSCs). During development, the decision to leave the self-renewing state and selection of a differentiation pathway is regulated by a number of transcription factors. Among them, genes GATA-1 and PU.1 form a core negative feedback module to regulate the genetic switching between the cell fate choices of HSCs. Although extensive experimental studies have revealed the mechanisms to regulate the expression of these two genes, it is still unclear how this simple module regulates the genetic switching.
methodsIn this work we proposed a mathematical model to study the mechanisms of the GATA-PU.1 gene network in the determination of HSC differentiation pathways. We incorporated the mechanisms of GATA switch into the module, and developed a mathematical model that comprises three genes GATA-1, GATA-2 and PU.1. In addition, a novel multiple-objective optimization method was designed to infer unknown parameters in the proposed model by realizing different experimental observations. A stochastic model was also designed to describe the critical function of noise, due to the small copy numbers of molecular species, in determining the differentiation pathways.
resultsThe proposed deterministic model has successfully realized three stable steady states representing the priming and different progenitor cells as well as genetic switching between the genetic states under various experimental conditions. Using different values of GATA-1 synthesis rate for the GATA-1 protein availability in the chromatin sites during the time period of GATA switch, stochastic simulations for the first time have realized different proportions of cells leading to different developmental pathways under various experimental conditions.
conclusionsMathematical models provide testable predictions regarding the mechanisms and conditions for realizing different differentiation pathways of hematopoietic stem cells. This work represents the first attempt at using a discrete stochastic model to realize the decision of HSC differentiation pathways showing a multimodal distribution.
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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.