title: Renewal of the Holocrine Meibomian Glands by Label-Retaining, Unipotent Epithelial Progenitors.
abstract: 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, K14CreER(T2)-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.
authors: The Gavin Herbert Eye Institute, University of California Irvine, 843 Health Sciences Road, Irvine, CA 92697-4390, USA.
authors: Geraint J
authors: GJ
authors: Parfitt
authors: The School of Optometry & Vision Sciences, Cardiff University, Maindy Road, Cardiff CF24 4HQ, UK.
authors: Phillip N
authors: PN
authors: Lewis
authors: The School of Optometry & Vision Sciences, Cardiff University, Maindy Road, Cardiff CF24 4HQ, UK.
authors: Robert D
authors: RD
authors: Young
authors: School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors: Alex
authors: A
authors: Richardson
authors: Centenary Institute and Discipline of Dermatology, Bosch Institute, Sydney Medical School, University of Sydney, Sydney, NSW 2050, Australia.
authors: J Guy
authors: JG
authors: Lyons
authors: School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
authors: Nick
authors: N
authors: Di Girolamo
authors: The Gavin Herbert Eye Institute, University of California Irvine, 843 Health Sciences Road, Irvine, CA 92697-4390, USA. Electronic address: jjester@uci.edu.
authors: James V
authors: JV
authors: Jester
mesh_terms: D000818:Animals; D015415:Biomarkers; D002454:Cell Differentiation; D019070:Cell Lineage; D015870:Gene Expression; D017930:Genes, Reporter; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D008537:Meibomian Glands / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D053547:Keratin-14
keywords: 3D reconstruction; H2B-GFP/K5tTA; adult stem cells; meibomian gland