ArticleMolecular systems biology2017
Biphasic response as a mechanism against mutant takeover in tissue homeostasis circuits.
Article in Molecular systems biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
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- A novel simple disposition index (SPINA-DI) from fasting insulin and glucose concentration as a robust measure of carbohydrate homeostasis.Journal of diabetes · 2024Article
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- A New Perspective on Regulation of Pituitary Plasticity: The Network of SOX2-Positive Cells May Coordinate Responses to Challenge.Endocrinology · 2022Article
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- A Mechanism for Ovulation Number Control.Frontiers in endocrinology · 2022Article
- Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion.Frontiers in endocrinology · 2022Review
- Design patterns for engineering genetic stability.Current opinion in biomedical engineering · 2021Article
- Programmable protein circuit design.Cell · 2021Review
- Senescent cells and the incidence of age-related diseases.Aging cell · 2021Article
- A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks.Molecular systems biology · 2020Article
- Endocrine Autoimmune Disease as a Fragility of Immune Surveillance against Hypersecreting Mutants.Immunity · 2020Article
- Heterogeneity and Delayed Activation as Hallmarks of Self-Organization and Criticality in Excitable Tissue.Frontiers in physiology · 2019Article
- Article
- Biphasic response as a mechanism against mutant takeover in tissue homeostasis circuits.Molecular systems biology · 2017Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissues use feedback circuits in which cells send signals to each other to control their growth and survival. We show that such feedback circuits are inherently unstable to mutants that misread the signal level: Mutants have a growth advantage to take over the tissue, and cannot be eliminated by known cell-intrinsic mechanisms. To resolve this, we propose that tissues have biphasic responses in and the signal is toxic at both high and low levels, such as glucotoxicity of beta cells, excitotoxicity in neurons, and toxicity of growth factors to T cells. This gives most of these mutants a frequency-dependent selective disadvantage, which leads to their elimination. However, the biphasic mechanisms create a new unstable fixed point in the feedback circuit beyond which runaway processes can occur, leading to risk of diseases such as diabetes and neurodegenerative disease. Hence, glucotoxicity, which is a dangerous cause of diabetes, may have a protective anti-mutant effect. Biphasic responses in tissues may provide an evolutionary stable strategy that avoids invasion by commonly occurring mutants, but at the same time cause vulnerability to disease.
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