Tanida Sakurako, Fuji Kana, Lu Linjie, Guyomar Tristan, Lee Byung Ho, Honigmann Alf, Grapin-Botton Anne, Riveline Daniel, Hiraiwa Tetsuya, Nonomura Makiko, Sano Masaki
Universal Biology Institute, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
PLoS Comput Biol. 2025 Aug 18;21(8):e1012090. doi: 10.1371/journal.pcbi.1012090. eCollection 2025 Aug.
Organoids are ideal systems to predict the phenotypes of organs. However, there is currently a lack of understanding regarding the generalized rules that enable use of simple cellular principles to make morphological predictions of entire organoids. Therefore, we employed a phase field model with the following basic components: the minimum conditions for the timing and volume of cell division, lumen nucleation rules, and lumenal pressure. Through our model, we could compute and generate a myriad of organoid phenotypes observed till date. We propose morphological indices necessary to characterize the shapes and construct phase diagrams and show their dependencies on proliferation time and lumen pressure. Additionally, we introduced the lumen-index parameter, which helped in examining the criteria to maintain organoids as spherical structures comprising a single layer of cells and enclosing an intact lumen. Finally, we predict a star-like organoid phenotype that did not undergo differentiation, suggesting that the volume constraint during cell division may determine the final phenotype. In summary, our approach provides researchers with guidelines to test the mechanisms of self-organization and predict the shape of organoid.
类器官是预测器官表型的理想系统。然而，目前对于能够利用简单细胞原理对整个类器官进行形态学预测的通用规则尚缺乏了解。因此，我们采用了一个相场模型，其具有以下基本组成部分：细胞分裂的时间和体积的最小条件、管腔成核规则以及管腔内压力。通过我们的模型，我们能够计算并生成迄今为止观察到的无数类器官表型。我们提出了表征形状所需的形态学指标并构建相图，展示了它们对增殖时间和管腔内压力的依赖性。此外，我们引入了管腔指数参数，这有助于研究将类器官维持为包含单层细胞并包围完整管腔的球形结构的标准。最后，我们预测了一种未发生分化的星状类器官表型，这表明细胞分裂期间的体积限制可能决定最终表型。总之，我们的方法为研究人员提供了测试自组织机制和预测类器官形状的指导方针。
