Bistability and hysteresis in cell fate switches
Bistability means a system has two stable states. Hysteresis means its state depends on the route by which an input was reached. Later texts use it for gene circuits and cell fate. Later authors tie both to memory and to a point of no return between two outcomes.379
- Earliest held
- 1902, Bose, J. C.
- Most discussed in
- Adaptive response of a gene network to…, 2006
- In the library
- 367 passages in 71 works
- Rewritten
- 2026-10-26
Early uses of hysteresis
Bose (1902) noted that preliminary stimulation increases later responsiveness, and he plotted a cyclic curve to show hysteresis.1 Loeb (1912) used the term for something else. He proposed "associative hysteresis" as a preferable name for associative memory, and he wanted animals for his instinct experiments whose reactions it did not complicate.2 Bayliss (1915) gave a physical case. A gel's water content at a given vapour tension shows whether the gel was earlier exposed to rising or falling tension.3 He concluded that inorganic systems have time factors and life histories. Bose (1928) reported that plant responses after a cycle of experiments differ from those at the start, and he attributed this to physiological hysteresis.4
Attractors in gene circuits
Kashiwagi and colleagues (2006) worked with a two-operon gene network. When total gene products were high, the network entered a bistable regime with two attractors. A small excess of one repressor suppressed the other operon, and cells were tipped into one of two self-stabilizing states.5 Balaskas and colleagues (2012) analysed a circuit that reads the Sonic Hedgehog gradient. Their simulations suggested hysteresis in Nkx2.2. Once N was active, a lower signal level sufficed to maintain it than to induce it.6 They also found parameter sets that oscillated instead. Sorek, Balaban and Loewenstein (2013) said that bistability naturally emerges when positive feedback and saturation are present, and they treated it as a basis for memory in gene networks.7
Bistability in membrane voltage
Law and Levin (2015) simulated resting-potential bistability in amphibian and mammalian cell models. Both model types showed bistability, but they needed different ion channel subsets.8 Persistent sodium helped in the mammalian case, and inward-rectifying potassium helped in the amphibian oocyte case. In amphibians, potassium channels of the Kv1.x and Kv2.x families tended to disrupt the bistable memory.8 Cervera and colleagues (2016) argued that membrane potential bistability is not required for coupling genetic and bioelectrical signalling. They noted that it gives a clear distinction between single-cell states in a spatial pattern of potentials.
Point of no return
Zakirov and colleagues (2021) applied the idea to tip and stalk selection in angiogenesis. They used a ball-on-landscape analogy, in which two valleys stand for the two cell fates and a hill between them stands for the barrier. They proposed that filopodia help generate that hill. They also defined when the system has passed the point of no return into one attractor.9 Their working rule was a lead of 600 Dll4 ligands held for 100 time steps. They called this method heuristic, and it assumes the bistable dynamics found earlier in the paper and the absence of long-timescale fluctuations.9
Allusion has already been made to the increased responsiveness conferred by preliminary stimulation (see p. 127).
Bose, J. C., 1902 · Response in the Living and Non-Living · open at passage 260associative memory or, as it may preferably be termed, associative hysteresis
Loeb, J., 1912 · The Mechanistic Conception of Life · open at passage 386we have information as to whether the previous history has been one of exposure to increasing or to decreasing tension of water vapour.
Bayliss, W. M., 1915 · Principles of General Physiology · open at passage 37Owing to pl^siological hysteresis , the response after a cycle of experiments is not exactly the same as at the beginning.
Bose, J. C., 1928 · The Motor Mechanism of Plants · open at passage 641Thus, the cells are tipped into either of the two self-stabilizing Attractors 1 and 2, as originally intended by the circuit design.
Kashiwagi A, Urabe I, Kaneko K, Yomo T, 2006 · Adaptive response of a gene network to environmental changes by fitness-induced… · open at passage 7Accordingly, the value of G necessary to maintain N, once activated, was lower than that needed to initially induce N.
Balaskas N, Ribeiro A, Panovska J, Dessaud E, Sasai N, Page…, 2012 · Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the… · open at passage 22Bistability naturally emerges in dynamical systems if two conditions are fulfilled: positive feedback and saturation
Sorek M, Balaban NQ, Loewenstein Y, 2013 · Stochasticity, bistability and the wisdom of crowds: a model for associative… · open at passage 8We find that typical mammalian models and amphibian oocyte models exhibit bistability when expressing different ion channel subsets
Law R, Levin M, 2015 · Bioelectric memory: modeling resting potential bistability in amphibian embryos… · open at passage 2determine the earliest time indicator of when the dynamical system has gone past the point of no return into the attractor of tip versus stalk.
Zakirov B, Charalambous G, Thuret R, Aspalter IM…, 2021 · Active perception during angiogenesis: filopodia speed up Notch selection of… · open at passage 93