Reprogramming, oscillations and transdifferentiation in epigenetic landscapes

Kaity, Bivash; Sarkar, Ratan; Chakrabarti, Buddhapriya; Mitra, Mithun K.

doi:10.1038/s41598-018-25556-9

Cited by 16 publications

(14 citation statements)

References 71 publications

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“…more than two fates) might generically be generated, in a way that allows differentiation to be biased towards locally-favourable outcomes. We note this is a topic of much current interest in systems biology, particularly noting the exploration of connections between GRN topology and oscillatory dynamics [12], generic links with differentiation dynamics [13][14][15], and e.g. reshaping the epigenetic landscape by rewiring the GRN using cross-repression among transcription factors (TFs) with self-regulation [14].…”

Section: Introductionmentioning

confidence: 99%

Novel Generic Models for Differentiating Stem Cells Reveal Oscillatory Mechanisms

Farjami

Sosa

Dawes

et al. 2021

Preprint

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Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically-motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington's epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.

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Section: Introductionmentioning

confidence: 99%

Novel Generic Models for Differentiating Stem Cells Reveal Oscillatory Mechanisms

Farjami

Sosa

Dawes

et al. 2021

Preprint

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“…The dynamics of a toggle switch can be influenced by gene expression noise [39], epigenetic changes [40], partitioning errors during cell division [41][42][43][44], and conformational noise in intrinsically disordered regions of a component in a switch [45]. Thus, the deterministic and stochastic dynamics of toggle switches and coupling of many positive and negative feedback loops have been well-explored in many biological systems [19,20,[46][47][48][49][50][51], including spatially extended realizations such as diffusion of mutually inhibiting molecules [52], and synthetic design of circuits to achieve a set of desired functions [53,54].…”

Section: Discussionmentioning

confidence: 99%

Operating principles of circular toggle polygons

Hati

Duddu

Jolly

2020

Preprint

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Decoding the dynamics of cellular decision-making and cell differentiation is a central question in cell and developmental biology. A common network motif involved in many cell-fate decisions is a mutually inhibitory feedback loop between two self-activating ‘master regulators’ A and B, also called as toggle switch. Typically, it can allow for three stable states – (high A, low B), (low A, high B) and (medium A, medium B). A toggle triad – three mutually repressing regulators A, B and C, i.e. three toggle switches arranged circularly (between A and B, between B and C, and between A and C) – can allow for six stable states: three ‘single positive’ and three ‘double positive’ ones. However, the operating principles of larger toggle polygons, i.e. toggle switches arranged circularly to form a polygon, remain unclear. Here, we simulate using both discrete and continuous methods the dynamics of different sized toggle polygons. We observed a pattern in their steady state frequency depending on whether the polygon was an even or odd numbered one. The even-numbered toggle polygons result in two dominant states with consecutive components of the network expressing alternating high and low levels. The odd-numbered toggle polygons, on the other hand, enable more number of states, usually twice the number of components with the states that follow ‘circular permutation’ patterns in their composition. Incorporating self-activations preserved these trends while increasing the frequency of multistability in the corresponding network. Our results offer insights into design principles of circular arrangement of regulatory units involved in cell-fate decision making, and can offer design strategies for synthesizing genetic circuits.

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“…more than two fates) might generically be generated, in a way that allows differentiation to be biased towards locally favourable outcomes [11]. We note this is a topic of much current interest in systems biology, particularly noting the exploration of connections between GRN topology and oscillatory dynamics [12,13], generic links with differentiation dynamics [14][15][16], and e.g. reshaping the epigenetic landscape by rewiring the GRN using cross-repression among transcription factors (TFs) with self-regulation [15].…”

Section: Introductionmentioning

confidence: 99%

Novel generic models for differentiating stem cells reveal oscillatory mechanisms

Farjami

Sosa

Dawes

et al. 2021

J. R. Soc. Interface.

View full text Add to dashboard Cite

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington’s epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario, gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario, two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.

show abstract

Reprogramming, oscillations and transdifferentiation in epigenetic landscapes

Cited by 16 publications

References 71 publications

Novel Generic Models for Differentiating Stem Cells Reveal Oscillatory Mechanisms

Novel Generic Models for Differentiating Stem Cells Reveal Oscillatory Mechanisms

Operating principles of circular toggle polygons

Novel generic models for differentiating stem cells reveal oscillatory mechanisms

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