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Dev Cell. 2017 Sep 25;42(6):600-615.e4. doi: 10.1016/j.devcel.2017.08.024.

Tension Creates an Endoreplication Wavefront that Leads Regeneration of Epicardial Tissue.

Author information

1
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA.
2
Regeneration Next, Duke University, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
3
Department of Biology, Duke University, Durham, NC 27708, USA.
4
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14624, USA; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14624, USA.
5
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
6
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14624, USA; Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14624, USA; Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14624, USA.
7
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Regeneration Next, Duke University, Durham, NC 27710, USA. Electronic address: kenneth.poss@duke.edu.

Abstract

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.

KEYWORDS:

endoreplication; epicardium; heart; mechanical tension; polyploidy; regeneration; zebrafish

PMID:
28950101
PMCID:
PMC5645043
DOI:
10.1016/j.devcel.2017.08.024
[Indexed for MEDLINE]
Free PMC Article

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