Xie Gengqiang, Modak Chaity, Usman Olalekan H, Tan Raphael W F, Coca Nicole, De Jesus Gabriela, Wang Yue Julia, Thirumalai D, Li Xin, Irianto Jerome
Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL, USA.
Department of Chemistry, University of Texas at Austin, Austin, TX, USA.
Commun Biol. 2025 Dec 5;8(1):1749. doi: 10.1038/s42003-025-09136-y.
Rotational migration is one specific form of collective cell migration when epithelial cells are confined in a spherical geometry, such as in the epithelial acini. This tissue-level rotation motion is crucial for the morphogenesis of multiple epithelial systems. Here, we introduce human pancreatic ductal organoids as a model to study rotational migration. Live imaging revealed the persistent rotation of the organoids over time. By tracking the nuclei, the three-dimensional trajectory of the cellular movement was reconstructed and the velocity of the rotation was quantified. The presence of focal adhesion clusters and prominent actin stress fibers were observed at the basal side of the organoids, suggesting the interactions between the cells and the surrounding extracellular matrix. Finally, our inhibition study showed the dependence of pancreatic ductal organoid rotational migration on myosin activity, actin polymerization, and actin branching. We hope that this model will enable future studies with human primary cells, which are more faithful to normal epithelial cells.
旋转迁移是上皮细胞被限制在球形结构中(如上皮腺泡)时集体细胞迁移的一种特定形式。这种组织水平的旋转运动对多个上皮系统的形态发生至关重要。在此,我们引入人胰腺导管类器官作为研究旋转迁移的模型。实时成像显示类器官随时间持续旋转。通过追踪细胞核,重建了细胞运动的三维轨迹并量化了旋转速度。在类器官的基底侧观察到粘着斑簇和明显的肌动蛋白应力纤维的存在,表明细胞与周围细胞外基质之间的相互作用。最后,我们的抑制研究表明胰腺导管类器官的旋转迁移依赖于肌球蛋白活性、肌动蛋白聚合和肌动蛋白分支。我们希望这个模型将有助于未来对人原代细胞的研究,这些细胞更接近正常上皮细胞。