Mechanical control of cell proliferation patterns in growing tissues.
Mechanical control of cell proliferation patterns in growing tissues.
复制标题
生长组织中细胞增殖模式的机械控制。
DOI：
10.1101/2023.07.25.550581
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Banerjee,Shiladitya
中科院分区：
文献类型：
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作者：
Carpenter,LoganC;Pérez-Verdugo,Fernanda;Banerjee,Shiladitya
细胞增殖在调节组织稳态和发育中起着至关重要的作用。然而，我们对细胞增殖在密集组织中是如何控制的理解是有限的。在这里，我们开发了一个计算框架来预测生长组织中细胞增殖的模式，将单细胞行为和细胞-细胞相互作用与组织水平的生长联系起来。我们的模型结合了控制细胞生长，分裂和消除的概率规则，同时还考虑了它们与组织力学的反馈。特别地，在高细胞密度的区域中，细胞生长被抑制并且细胞凋亡被增强。这些规则和模型参数使用实验数据校准，我们预测组织约束如何影响细胞大小和增殖动力学，以及单细胞的物理特性如何影响组织生长的时空模式。我们的研究结果表明，组织约束和细胞生长之间的机械反馈导致组织边界处的细胞增殖增强，而批量中的细胞生长被阻止。通过调节细胞弹性和接触抑制增殖，我们可以调节细胞增殖的出现模式，从低接触抑制下的均匀生长到高接触抑制下的局部生长。此外，组织的机械状态支配组织生长的动力学，其中影响组织压力的细胞参数在确定总体生长速率中起重要作用。因此，我们的计算研究强调了细胞力学性质对生长组织中细胞增殖的时空模式的影响。
Cell proliferation plays a crucial role in regulating tissue homeostasis and development. However, our understanding of how cell proliferation is controlled in densely packed tissues is limited. Here we develop a computational framework to predict the patterns of cell proliferation in growing tissues, connecting single-cell behaviors and cell-cell interactions to tissue-level growth. Our model incorporates probabilistic rules governing cell growth, division, and elimination, while also taking into account their feedback with tissue mechanics. In particular, cell growth is suppressed and apoptosis is enhanced in regions of high cell density. With these rules and model parameters calibrated using experimental data, we predict how tissue confinement influences cell size and proliferation dynamics, and how single-cell physical properties influence the spatiotemporal patterns of tissue growth. Our findings indicate that mechanical feedback between tissue confinement and cell growth leads to enhanced cell proliferation at tissue boundaries, whereas cell growth in the bulk is arrested. By tuning cellular elasticity and contact inhibition of proliferation we can regulate the emergent patterns of cell proliferation, ranging from uniform growth at low contact inhibition to localized growth at higher contact inhibition. Furthermore, mechanical state of the tissue governs the dynamics of tissue growth, with cellular parameters affecting tissue pressure playing a significant role in determining the overall growth rate. Our computational study thus underscores the impact of cell mechanical properties on the spatiotemporal patterns of cell proliferation in growing tissues.