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

Developmental cell | Sep 25, 2017

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.

Pubmed ID: 28950101 RIS Download

Mesh terms: Animals | Biomechanical Phenomena | Cell Movement | Endoreduplication | Giant Cells | Hypertrophy | Mice, Inbred C57BL | Mitosis | Pericardium | Polyploidy | Regeneration | Zebrafish

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Associated grants

  • Agency: NICHD NIH HHS, Id: R00 HD074670
  • Agency: NHLBI NIH HHS, Id: R01 HL132389
  • Agency: NHLBI NIH HHS, Id: R01 HL131319
  • Agency: NIGMS NIH HHS, Id: T32 GM007184
  • Agency: NIGMS NIH HHS, Id: R01 GM033830
  • Agency: NHLBI NIH HHS, Id: R01 HL081674
  • Agency: NHLBI NIH HHS, Id: R01 HL120919
  • Agency: NHLBI NIH HHS, Id: T32 HL066988

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