ArticleNPJ systems biology and applications2022
A robust method for designing multistable systems by embedding bistable subsystems.
Article in NPJ systems biology and applications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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Who cites it
5 citing papers in PubMed.
- Cell Lineage Affiliation During Hematopoiesis.International journal of molecular sciences · 2025Review
- A method for in silico exploration of potential glioblastoma multiforme attractors using single-cell RNA sequencing.Scientific reports · 2024Article
- Hematopoietic and Chronic Myeloid Leukemia Stem Cells: Multi-Stability versus Lineage Restriction.International journal of molecular sciences · 2022Review
- The Social Norm of Hematopoietic Stem Cells and Dysregulation in Leukemia.International journal of molecular sciences · 2022Review
- Lessons to cancer from studies of leukemia and hematopoiesis.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although multistability is an important dynamic property of a wide range of complex systems, it is still a challenge to develop mathematical models for realising high order multistability using realistic regulatory mechanisms. To address this issue, we propose a robust method to develop multistable mathematical models by embedding bistable models together. Using the GATA1-GATA2-PU.1 module in hematopoiesis as the test system, we first develop a tristable model based on two bistable models without any high cooperative coefficients, and then modify the tristable model based on experimentally determined mechanisms. The modified model successfully realises four stable steady states and accurately reflects a recent experimental observation showing four transcriptional states. In addition, we develop a stochastic model, and stochastic simulations successfully realise the experimental observations in single cells. These results suggest that the proposed method is a general approach to develop mathematical models for realising multistability and heterogeneity in complex systems.
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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 Socratic graph.