Mechanisms of Disease and Translational Research, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Biomedical Imaging Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia.
Stem Cell Reports. 2019 Jan 8;12(1):14-28. doi: 10.1016/j.stemcr.2018.11.014. Epub 2018 Dec 13.
It is thought that corneal epithelial injuries resolve by leading-edge cells "sliding" or "rolling" into the wound bed. Here, we challenge this notion and show by real-time imaging that corneal wounds initially heal by "basal cell migration." The K14CreER-Confetti multi-colored reporter mouse was employed to spatially and temporally fate-map cellular behavior during corneal wound healing. Keratin-14 basal epithelia are forced into the wound bed by increased population pressure gradient from the limbus to the wound edge. As the defect resolves, centripetally migrating epithelia decelerate and replication in the periphery is reduced. With time, keratin-14-derived clones diminish in number concomitant with their expansion, indicative that clonal evolution aligns with neutral drifting. These findings have important implications for the involvement of stem cells in acute tissue regeneration, in key sensory tissues such as the cornea.
人们认为角膜上皮损伤通过前缘细胞“滑动”或“滚动”进入伤口床得以修复。在这里，我们通过实时成像挑战了这一观点，并表明角膜伤口最初通过“基底细胞迁移”来愈合。K14CreER-Confetti 多色报告小鼠被用于在角膜伤口愈合过程中时空追踪细胞行为。角蛋白 14 基底上皮受到来自角膜缘到伤口边缘的人口压力梯度增加的推动而进入伤口床。随着缺陷的解决，向心性迁移的上皮减速，周边的复制减少。随着时间的推移，角蛋白 14 衍生的克隆数量减少，同时其扩张，表明克隆进化与中性漂移一致。这些发现对于干细胞在急性组织再生中的参与具有重要意义，特别是在角膜等关键感觉组织中。
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