研究人员描述了在细胞培养中从上皮单层中出现的领头细胞，发现它们激活了压力传感器p53，这足以启动领头细胞的行为。p53激活细胞周期抑制因子p21WAF1/CIP1，从而反过来通过抑制细胞周期素依赖的激酶活性来诱导领头行为。因此，机械诱导的p53指导出现了短暂的领头细胞群，驱动迁移并确保在上皮修复时清除它们。
据介绍，上皮细胞跨越伤口迁移来修复受伤的组织。处于迁移片前部的领头细胞经常驱动这一过程。然而，目前还不清楚领头细胞是如何从表面上同质的上皮细胞群中出现的。
附：英文原文
Title: p53 directs leader cell behavior, migration, and clearance during epithelial repair
Author: Kasia Kozyrska, Giulia Pilia, Medhavi Vishwakarma, Laura Wagstaff, Maja Goschorska, Silvia Cirillo, Saad Mohamad, Kelli Gallacher, Rafael E. Carazo Salas, Eugenia Piddini
Issue&Volume: 2022-02-11
Abstract: Epithelial cells migrate across wounds to repair injured tissue. Leader cells at the front of migrating sheets often drive this process. However, it is unclear how leaders emerge from an apparently homogeneous epithelial cell population. We characterized leaders emerging from epithelial monolayers in cell culture and found that they activated the stress sensor p53, which was sufficient to initiate leader cell behavior. p53 activated the cell cycle inhibitor p21WAF1/CIP1, which in turn induced leader behavior through inhibition of cyclin-dependent kinase activity. p53 also induced crowding hypersensitivity in leader cells such that, upon epithelial closure, they were eliminated by cell competition. Thus, mechanically induced p53 directs emergence of a transient population of leader cells that drive migration and ensures their clearance upon epithelial repair.
DOI: abl8876
Source: https://www.science.org/doi/10.1126/science.abl8876