Cell cycle criticality as a mechanism for robust cell population control
File(s)
Published version
Author(s)
Simons, Benjmain David
Karin, Omer
Type
Journal Article
Abstract
Tissue homeostasis requires a precise balance between stem cell self-renewal and differentiation. While fate decisions are known to be closely linked with cell cycle progression, the functional significance of this relationship is unclear. We propose a mechanistic framework to analyse cellular dynamics when cell fate is coupled to cell cycle duration. Our model highlights a unique aspect of cell cycle regulation where mitogens serve as control parameters for a bifurcation governing the G1-S transition. Under competitive feedback from cell-cell interactions, the cell cycle regulatory network fine-tunes near the critical point of this bifurcation. Critical positioning lengthens G1 while amplifying cell-to-cell variability in mitogenic signalling and biochemical states. Such regulation confers significant advantages for controlling cell population dynamics, with alternative topologies enabling rapid tissue growth and repair or efficient mutant rejection. Counter-intuitively, we propose that stem cells may couple prolonged G1 with increased self-renewal propensity to efficiently suppress mis-sensing mutants. Our theory provides a distinct explanation to puzzling dynamical and statistical patterns of G1 lengthening and predicts regulatory strategies across development, homeostasis, and ageing.
Date Issued
2026-02-02
Date Acceptance
2025-10-01
Citation
Molecular Systems Biology, 2026, 22 (2), pp.241-258
ISSN
1744-4292
Publisher
Springer Nature
Start Page
241
End Page
258
Journal / Book Title
Molecular Systems Biology
Volume
22
Issue
2
Copyright Statement
© The Author(s) Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.
License URL
Publication Status
Published
Date Publish Online
2025-11-06