Stochasticity and determinism in cell fate decisions

Zechner, Christoph; Nerli, Elisa; Norden, Caren

doi:10.1242/dev.181495

Cited by 48 publications

(47 citation statements)

References 69 publications

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“…The advance of imaging techniques, image analysis algorithms, and the possibility of performing backtracking studies in the retina are exciting emerging tools to follow similar questions in future studies. Such sophisticated studies will in turn promote our understanding of reproducibility and/or plasticity of lineage decisions at diverse developmental stages in different tissues of the CNS ( Zechner et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway

Nerli

Rocha-Martins

Norden

2020

eLife

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During brain development, progenitor cells need to balance proliferation and differentiation in order to generate different neurons in the correct numbers and proportions. Currently, the patterns of multipotent progenitor divisions that lead to neurogenic entry and the factors that regulate them are not fully understood. We here use the zebrafish retina to address this gap, exploiting its suitability for quantitative live-imaging. We show that early neurogenic progenitors arise from asymmetric divisions. Notch regulates this asymmetry, as when inhibited, symmetric divisions producing two neurogenic progenitors occur. Surprisingly however, Notch does not act through an apicobasal activity gradient as previously suggested, but through asymmetric inheritance of Sara-positive endosomes. Further, the resulting neurogenic progenitors show cell biological features different from multipotent progenitors, raising the possibility that an intermediate progenitor state exists in the retina. Our study thus reveals new insights into the regulation of proliferative and differentiative events during central nervous system development.

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Section: Discussionmentioning

confidence: 99%

Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway

Nerli

Rocha-Martins

Norden

2020

eLife

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“…Computational and experimental approaches have been used to study stochasticity in biological systems (Meyer and Roeder 2014 ). For example, a recent review on stochasticity in cellular fate decisions compared it to a weighted coin toss (Zechner et al 2020 ). We have now begun to understand the mechanisms underlying the figurative coin toss model and to identify the factors contributing to the associated coin weights in various developmental processes.…”

Section: Stochasticity In Plant Developmentmentioning

confidence: 99%

“…Variability in gene expression is not the only source of phenotypic variations. Examples from animals have shown that mechanical properties of cells and molecular fluctuations in the dynamics of signaling pathways affect cellular fate decision (Kroll et al 2020 ; Weinreb et al 2020 ; Zechner et al 2020 ). Significant advancements have been made in research on stochasticity in cellular size and patterning (Meyer and Roeder 2014 ).…”

Section: Stochasticity In Plant Developmentmentioning

confidence: 99%

Developmental stochasticity and variation in floral phyllotaxis

Kitazawa

2021

J Plant Res

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Floral phyllotaxis is a relatively robust phenotype; trimerous and pentamerous arrangements are widely observed in monocots and core eudicots. Conversely, it also shows variability in some angiosperm clades such as ‘ANA’ grade (Amborellales, Nymphaeales, and Austrobaileyales), magnoliids, and Ranunculales. Regardless of the phylogenetic relationship, however, phyllotactic pattern formation appears to be a common process. What are the causes of the variability in floral phyllotaxis and how has the variation of floral phyllotaxis contributed to floral diversity? In this review, I summarize recent progress in studies on two related fields to develop answers to these questions. First, it is known that molecular and cellular stochasticity are inevitably found in biological systems, including plant development. Organisms deal with molecular stochasticity in several ways, such as dampening noise through gene networks or maintaining function through cellular redundancy. Recent studies on molecular and cellular stochasticity suggest that stochasticity is not always detrimental to plants and that it is also essential in development. Second, studies on vegetative and inflorescence phyllotaxis have shown that plants often exhibit variability and flexibility in phenotypes. Three types of phyllotaxis variations are observed, namely, fluctuation around the mean, transition between regular patterns, and a transient irregular organ arrangement called permutation. Computer models have demonstrated that stochasticity in the phyllotactic pattern formation plays a role in pattern transitions and irregularities. Variations are also found in the number and positioning of floral organs, although it is not known whether such variations provide any functional advantages. Two ways of diversification may be involved in angiosperm floral evolution: precise regulation of organ position and identity that leads to further specialization of organs and organ redundancy that leads to flexibility in floral phyllotaxis.

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“…Heterogeneity in cell populations may originate from deterministic or stochastic processes. For example, the observed distribution of cell cycle durations in a population of cells is governed either by stochastic processes, inherited in a deterministic fashion, or some combination of both [3][4][5][6] (Figure 1A). Previous studies have shown poor correlations within lineages when observing direct ancestral relationships, but remain correlated with immediate relatives 4,7,8 .…”

Section: Introductionmentioning

confidence: 99%

Automated deep lineage tree analysis using a Bayesian single cell tracking approach

Ulicna

Vallardi

Charras

et al. 2020

Preprint

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Single-cell methods are beginning to reveal the intrinsic heterogeneity in cell populations, which arises from the interplay or deterministic and stochastic processes. For example, the molecular mechanisms of cell cycle control are well characterised, yet the observed distribution of cell cycle durations in a population of cells is heterogenous. This variability may be governed either by stochastic processes, inherited in a deterministic fashion, or some combination of both. Previous studies have shown poor correlations within lineages when observing direct ancestral relationships but remain correlated with immediate relatives. However, assessing longer-range dependencies amid noisy data requires significantly more observations, and demands the development of automated procedures for lineage tree reconstruction. Here, we developed an open-source Python library, btrack, to facilitate retrieval of deep lineage information from live-cell imaging data. We acquired 3,500 hours of time-lapse microscopy data of epithelial cells in culture and used our software to extract 22,519 fully annotated single-cell trajectories. Benchmarking tests, including lineage tree reconstruction assessments, demonstrate that our approach yields high-fidelity results and achieves state-of-the-art performance without the requirement for manual curation of the tracker output data. To demonstrate the robustness of our supervision-free cell tracking pipeline, we retrieve cell cycle durations and their extended inter- and intra-generational family relationships, for up to eight generations, and up to fourth cousin relationships. The extracted lineage tree dataset represents approximately two orders of magnitude more data, and longer-range dependencies, than in previous studies of cell cycle heritability. Our results extend the range of observed correlations and suggest that strong heritable cell cycling is present. We envisage that our approach could be extended with additional live-cell reporters to provide a detailed quantitative characterisation of biochemical and mechanical origins to cycling heterogeneity in cell populations.

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Stochasticity and determinism in cell fate decisions

Cited by 48 publications

References 69 publications

Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway

Asymmetric neurogenic commitment of retinal progenitors involves Notch through the endocytic pathway

Developmental stochasticity and variation in floral phyllotaxis

Automated deep lineage tree analysis using a Bayesian single cell tracking approach

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