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神经嵴迁移与连续细胞状态。

Neural crest migration with continuous cell states.

机构信息

MCR Centre for Regenerative Medicine, University of Edinburgh, United Kingdom.

出版信息

J Theor Biol. 2019 Nov 21;481:84-90. doi: 10.1016/j.jtbi.2019.01.029. Epub 2019 Jan 29.

Abstract

Models of cranial neural crest cell migration in cell-induced (or self-generated) gradients have included a division of labour into leader and follower migratory states, which undergo chemotaxis and contact guidance, respectively. Despite validated utility of these models through experimental perturbation of migration in the chick embryo and gene expression analysis showing relevant heterogeneity at the single cell level, an often raised question has been whether the discrete cell states are necessary, or if a continuum of cell behaviours offers a functionally equivalent description. Here we argue that this picture is supported by recent single-cell transcriptome data. Motivated by this, we implement two versions of a continuous-state model: (1) signal choice and (2) signal combination. We find that the cell population migrates further than in the discrete-state model and than in experimental observations. We further show that the signal combination model, but not the signal choice model, can be successfully adjusted to experimentally plausible regimes by reducing the chemoattractant consumption parameter. Thus we show an equivalently plausible, experimentally motivated, model of neural crest cell migration.

摘要

颅神经嵴细胞在细胞诱导(或自我产生)梯度中的迁移模型包括将劳动分工为领导者和追随者迁移状态,分别经历趋化性和接触导向。尽管通过实验干扰鸡胚中的迁移和基因表达分析在单细胞水平上显示出相关的异质性验证了这些模型的有效性,但一个经常提出的问题是离散的细胞状态是否必要,或者连续的细胞行为是否提供了功能等效的描述。在这里,我们认为最近的单细胞转录组数据支持了这一观点。受此启发,我们实现了两种连续状态模型:(1)信号选择和(2)信号组合。我们发现细胞群体的迁移距离比离散状态模型和实验观察更远。我们进一步表明,信号组合模型(而不是信号选择模型)可以通过降低趋化因子消耗参数成功地调整到实验上合理的范围。因此,我们展示了一个同样合理的、具有实验动机的神经嵴细胞迁移模型。

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