Cell Fate Decision as High-Dimensional Critical State Transition

Mojtahedi, Mitra; Skupin, Alexander; Zhou, Joseph; Castano, Ivan G.; Leong-Quong, Rebecca Y. Y.; Chang, Hsie-Chia; Trachana, Kalliopi; Giuliani, Alessandro; Huang, Sui

doi:10.1371/journal.pbio.2000640

Cited by 308 publications

(347 citation statements)

References 50 publications

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“…Close to the critical point, which marks the transition from sender to receiver, the Notch-Delta channel has a poor performance. The latter informationtheoretic result is in agreement with previous results indicating the dynamical behaviour of differentiating cells when they undergo a critical state transition before fate selection [15].…”

Section: Cc-by-nc-ndsupporting

confidence: 93%

On the principles of cell decision-making: intracellular coupling improves cell responses fidelity of noisy signals

Reppas

Jorswieck

Hatzikirou

2017

Preprint

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Reliability of cell fate decision-making is crucial to biological development. Until today it has not been clear what are biology's design principles that allow for reliable cell decision making under the influence of noise. Here, we attempt to answer this question by drawing an analogy between cell decision-making and information theory. We show that coupling of intracellular signalling pathway networks makes cell phenotypic responses reliable for noisy signals. As a proof of concept, we show how cis-interaction of the Notch-Delta pathway allows for increased performance under the influence of noise. Interestingly, in this case, the coupling principle leads to an efficient energy management. Finally, our postulated principle offers a compelling argument why cellular encoding is organized in a non-linear and non-hierarchical manner.Intoduction.− Cell decisions are responses of cell's internal mechanisms to external signals [1]. Such mechanisms are typically termed as signal transduction pathways. Signal transduction occurs when an extracellular signalling molecule bounds to a certain receptor creating a complex. In turn, this complex of molecules triggers a biochemical chain of events inside the cell, leading to a phenotypic response [2]. These responses are required to be of high fidelity and reliability since they are related to vital organism processes, such as cellular metabolism, shape, differentiation, or mitotic activity [3].Signal transduction pathways can be considered as input-output communication channels. Each pathway involves a number of key interacting proteins. The chain of biochemical events that involves the reception, endocytosis, activation/inactivation, nucleus internalisation, degradation or exocytosis of such a protein defines a single processing channel, in terms of encoding and decoding. The network of interactions of these coupled proteinchannels defines the signal transduction channel.Signal transduction pathways are subject to noisy perturbations. Typically, intracellular or intrinsic noise corresponds to thermal/stochastic fluctuations of the involved protein interactions. Alternatively, it may also account for any unknown and unobserved protein. Extrinsic noise lumps phenomena that contribute to stochasticity in cell-cell or cell-microenvironment communication.In this paper, we seek answers on biology's design principles that allow for reliable cell decision-making under the influence of noise. By means of a minimalistic communication model, we show that channel coupling can enhance the information capacity. In turn, we focus on dynamic cell fate determination processes, such as the Notch-Delta pathway, by establishing an analogy with communication theoretical concepts. We show that pathway coupling improves the reliability of responses in noisy * haralampos.hatzikirou@helmholtz-hzi.de environments which, thus, can be considered as a mechanism for robust cell-decision making.From information theory to cell decision-making.− Cells can be viewed as decision-makers that constantly proce...

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Section: Cc-by-nc-ndsupporting

confidence: 93%

On the principles of cell decision-making: intracellular coupling improves cell responses fidelity of noisy signals

Reppas

Jorswieck

Hatzikirou

2017

Preprint

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“…Importantly, signalling entropy should not be confused with other transcriptional entropy measures, which are estimated over populations of single cells4546. For instance, the ‘transcriptional entropy' of Richard et al 45.…”

Section: Discussionmentioning

confidence: 99%

Single-cell entropy for accurate estimation of differentiation potency from a cell’s transcriptome

Teschendorff¹,

2017

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The ability to quantify differentiation potential of single cells is a task of critical importance. Here we demonstrate, using over 7,000 single-cell RNA-Seq profiles, that differentiation potency of a single cell can be approximated by computing the signalling promiscuity, or entropy, of a cell's transcriptome in the context of an interaction network, without the need for feature selection. We show that signalling entropy provides a more accurate and robust potency estimate than other entropy-based measures, driven in part by a subtle positive correlation between the transcriptome and connectome. Signalling entropy identifies known cell subpopulations of varying potency and drug resistant cancer stem-cell phenotypes, including those derived from circulating tumour cells. It further reveals that expression heterogeneity within single-cell populations is regulated. In summary, signalling entropy allows in silico estimation of the differentiation potency and plasticity of single cells and bulk samples, providing a means to identify normal and cancer stem-cell phenotypes.

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“…While differentiation is traditionally viewed as unidirectional and uniform, recent developments from single cell RNAseq analyses suggest that the differentiation trajectory is probabilistic [58,59]. Improvements in single cell analyses could be employed to analyze stochasticity and robustness of GRNs.…”

Section: Future Perspectives In the Endodermal Differentiation Grnmentioning

confidence: 99%

Uncovering Gene Regulatory Networks Controlling Plant Cell Differentiation

2017

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The development of multicellular organisms relies on the precise regulation of cellular differentiation. As such, there has been significant effort invested to understand the process through which an immature cell undergoes differentiation. In this review, we highlight key discoveries and advances that have contributed to our understanding of the transcriptional networks underlying Arabidopsis root endodermal differentiation. To conclude, we propose perspectives on how advances in molecular biology, microscopy and nucleotide sequencing will provide the tools to test the biological significance of these gene regulatory networks.

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Cell Fate Decision as High-Dimensional Critical State Transition

Cited by 308 publications

References 50 publications

On the principles of cell decision-making: intracellular coupling improves cell responses fidelity of noisy signals

On the principles of cell decision-making: intracellular coupling improves cell responses fidelity of noisy signals

Single-cell entropy for accurate estimation of differentiation potency from a cell’s transcriptome

Uncovering Gene Regulatory Networks Controlling Plant Cell Differentiation

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