期刊
DEVELOPMENTAL CELL
卷 42, 期 6, 页码 600-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2017.08.024
关键词
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资金
- American Heart Association (AHA) [14POST20230023, 16POST30230005]
- National Science Foundation (NSF) [2013126035, 2014175655]
- NIH [T32-GM007184, T32-HL066988-15, R00 HD074670, R01 HL120919, R01 GM033830, R01 HL132389, R01 HL131319, R01 HL081674]
- AHA [16PRE30490009, 15SDG25710444]
- Foundation Leducq
Mechanisms that control cell-cycle dynamics during tissue regeneration require elucidation. Here we find in zebrafish that regeneration of the epicardium, the mesothelial covering of the heart, is mediated by two phenotypically distinct epicardial cell subpopulations. These include a front of large, multinucleate leader cells, trailed by follower cells that divide to produce small, mononucleate daughters. By using live imaging of cell-cycle dynamics, we show that leader cells form by spatiotemporally regulated endoreplication, caused primarily by cytokinesis failure. Leader cells display greater velocities and mechanical tension within the epicardial tissue sheet, and experimentally induced tension anisotropy stimulates ectopic endoreplication. Unbalancing epicardial cell-cycle dynamics with chemical modulators indicated autonomous regenerative capacity in both leader and follower cells, with leaders displaying an enhanced capacity for surface coverage. Our findings provide evidence that mechanical tension can regulate cell-cycle dynamics in regenerating tissue, stratifying the source cell features to improve repair.
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