Emergent order in epithelial sheets by interplay of cell divisions and cell fate regulation.

IF 3.8 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

PLoS Computational Biology Pub Date : 2024-10-14 eCollection Date: 2024-10-01 DOI:10.1371/journal.pcbi.1012465

Philip Greulich

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引用次数: 0

Abstract

The fate choices of stem cells between self-renewal and differentiation are often tightly regulated by juxtacrine (cell-cell contact) signalling. Here, we assess how the interplay between cell division, cell fate choices, and juxtacrine signalling can affect the macroscopic ordering of cell types in self-renewing epithelial sheets, by studying a simple spatial cell fate model with cells being arranged on a 2D lattice. We show in this model that if cells commit to their fate directly upon cell division, macroscopic patches of cells of the same type emerge, if at least a small proportion of divisions are symmetric, except if signalling interactions are laterally inhibiting. In contrast, if cells are first 'licensed' to differentiate, yet retaining the possibility to return to their naive state, macroscopic order only emerges if the signalling strength exceeds a critical threshold: if then the signalling interactions are laterally inducing, macroscopic patches emerge as well. Lateral inhibition, on the other hand, can in that case generate periodic patterns of alternating cell types (checkerboard pattern), yet only if the proportion of symmetric divisions is sufficiently low. These results can be understood theoretically by an analogy to phase transitions in spin systems known from statistical physics.

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通过细胞分裂和细胞命运调控的相互作用，上皮细胞片中出现了秩序。

干细胞在自我更新和分化之间的命运选择往往受到并胞（细胞-细胞接触）信号的严格调控。在这里，我们通过研究一个将细胞排列在二维晶格上的简单空间细胞命运模型，评估细胞分裂、细胞命运选择和共生信号之间的相互作用如何影响自我更新上皮细胞片中细胞类型的宏观排序。我们在该模型中发现，如果细胞在分裂时直接决定其命运，那么至少有一小部分分裂是对称的，就会出现同一类型细胞的宏观斑块，除非信号相互作用具有横向抑制作用。相反，如果细胞首先被 "许可 "进行分化，但仍有可能回到幼稚状态，那么只有当信号强度超过临界阈值时，才会出现宏观秩序：如果信号相互作用是横向诱导性的，也会出现宏观斑块。另一方面，在这种情况下，侧向抑制可以产生周期性的细胞类型交替模式（棋盘模式），但前提是对称分裂的比例足够低。这些结果可以通过类比统计物理学中已知的自旋系统的相变从理论上加以理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PLoS Computational Biology BIOCHEMICAL RESEARCH METHODS-MATHEMATICAL & COMPUTATIONAL BIOLOGY

CiteScore

7.10

自引率

4.70%

发文量

820

审稿时长

2.5 months

期刊介绍： PLOS Computational Biology features works of exceptional significance that further our understanding of living systems at all scales—from molecules and cells, to patient populations and ecosystems—through the application of computational methods. Readers include life and computational scientists, who can take the important findings presented here to the next level of discovery. Research articles must be declared as belonging to a relevant section. More information about the sections can be found in the submission guidelines. Research articles should model aspects of biological systems, demonstrate both methodological and scientific novelty, and provide profound new biological insights. Generally, reliability and significance of biological discovery through computation should be validated and enriched by experimental studies. Inclusion of experimental validation is not required for publication, but should be referenced where possible. Inclusion of experimental validation of a modest biological discovery through computation does not render a manuscript suitable for PLOS Computational Biology. Research articles specifically designated as Methods papers should describe outstanding methods of exceptional importance that have been shown, or have the promise to provide new biological insights. The method must already be widely adopted, or have the promise of wide adoption by a broad community of users. Enhancements to existing published methods will only be considered if those enhancements bring exceptional new capabilities.