Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice

被引:167
作者
Park, Sangbum [1 ]
Gonzalez, David G. [1 ,2 ]
Guirao, Boris [3 ]
Boucher, Jonathan D. [1 ]
Cockburn, Katie [1 ]
Marsh, Edward D. [1 ]
Mesa, Kailin R. [1 ]
Brown, Samara [1 ]
Rompolas, Panteleimon [1 ]
Haberman, Ann M. [2 ]
Bellaiche, Yohanns [3 ]
Greco, Valentina [1 ,4 ,5 ]
机构
[1] Yale Sch Med, Dept Genet, New Haven, CT 06510 USA
[2] Yale Sch Med, Dept Immunobiol, Dept Lab Med, New Haven, CT 06510 USA
[3] CNRS, INSERM U934, Polar Div & Morphogenesis Team, Genet & Dev Biol Unit,UMR3215, F-75248 Paris 05, France
[4] Yale Sch Med, Yale Canc Ctr, Yale Stem Cell Ctr, Dept Cell Biol, New Haven, CT 06510 USA
[5] Yale Sch Med, Yale Canc Ctr, Yale Stem Cell Ctr, Dept Dermatol, New Haven, CT 06510 USA
基金
加拿大健康研究院; 美国国家卫生研究院; 欧洲研究理事会;
关键词
EPITHELIAL-CELLS; STEM-CELLS; IN-VITRO; SKIN; MIGRATION; REEPITHILIALIZATION; REEPITHELIALIZATION; MORPHOGENESIS; REGENERATION; INHIBITION;
D O I
10.1038/ncb3472
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Tissue repair is fundamental to our survival as tissues are challenged by recurrent damage. During mammalian skin repair, cells respond by migrating and proliferating to close the wound. However, the coordination of cellular repair behaviours and their effects on homeostatic functions in a live mammal remains unclear. Here we capture the spatiotemporal dynamics of individual epithelial behaviours by imaging wound re-epithelialization in live mice. Differentiated cells migrate while the rate of differentiation changes depending on local rate of migration and tissue architecture. Cells depart from a highly proliferative zone by directionally dividing towards the wound while collectively migrating. This regional coexistence of proliferation and migration leads to local expansion and elongation of the repairing epithelium. Finally, proliferation functions to pattern and restrict the recruitment of undamaged cells. This study elucidates the interplay of cellular repair behaviours and consequent changes in homeostatic behaviours that support tissue-scale organization of wound re-epithelialization.
引用
收藏
页码:155 / 163
页数:9
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