Visualizing the Contribution of Keratin-14+ Limbal Epithelial Precursors in Corneal Wound Healing

Visualizing the Contribution of Keratin-14+ Limbal Epithelial Precursors in Corneal Wound Healing.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: Stem Cell Reports
Volume: 12
Number: 1
Page Range: pp. 14-28
Date: 2019
Divisions: Immune Imaging
Depositing User: General Admin
Identification Number: 10.1016/j.stemcr.2018.11.014
ISSN: 22136711
Date Deposited: 15 Dec 2020 00:38

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 K14CreERT2-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.

Keywords: K14CreER(T2)-Confetti transgenic mice; basal cell migration; computational modeling; cornea wound healing; limbal epithelial stem cells; organ-culture system; spatiotemporal image correlation spectroscopy.

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Park, Mijeong
Richardson, Alexander
Pandzic, Elvis
Lobo, Erwin P.
Whan, Renee
Watson, Stephanie L.
Lyons, J. Guy
Wakefield, Denis
Di Girolamo, Nick
Last Modified: 15 Dec 2020 00:38

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