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Renewal of the holocrine meibomian glands by label-retaining, unipotent epithelial progenitors

Parfitt, Geraint J., Lewis, Phillip N. ORCID:, Young, Robert D. ORCID:, Richardson, Alex, Lyons, J. Guy, Di Girolamo, Nick and Jester, James V. 2016. Renewal of the holocrine meibomian glands by label-retaining, unipotent epithelial progenitors. Stem Cell Reports 7 (3) , pp. 399-410. 10.1016/j.stemcr.2016.07.010

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The meibomian and sebaceous glands secrete lipids to prevent desiccation of the ocular surface and skin, respectively. Precisely how these holocrine tissues regenerate is not well understood. To address this, we characterized keratin 5+ (K5) label-retaining cells (LRCs) and the lineage tracing of keratin 14 (K14) progenitors in mouse meibomian glands. Using the tet-off H2B-GFP/K5tTA mouse, H2B-GFP fluorescence dilutes 2-fold with every division in K5+ cell nuclei after doxycycline administration. In 3D reconstructions generated over a >28-day doxycycline chase, we observed LRCs at the acinus entrance where K6+ ductal epithelium terminates. For lineage tracing, K14CreERT2-Confetti mice were injected intraperitoneally with tamoxifen and euthanized at 23 and 59 weeks later. Meibomian gland acini in these mice were either monochromatic or dual-colored, whereas the duct exhibited multiple colors. In conclusion, LRCs are likely to direct meibomian gland turnover and may exist as two distinct unipotent progenitors that renew ductal and acinar tissue separately.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Subjects: R Medicine > RE Ophthalmology
Uncontrolled Keywords: 3D reconstruction, meibomian gland, adult stem cells, H2B-GFP/K5tTA
Additional Information: This is an open access article under the CC BY-NC-ND license
Publisher: Cell Press
ISSN: 2213-6711
Funders: Research to Prevent Blindness, Discovery Eye Foundation, NEI
Date of First Compliant Deposit: 30 March 2017
Date of Acceptance: 11 July 2016
Last Modified: 04 May 2023 18:15

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