Origin and Lineage Plasticity of Endogenous Lacrimal Gland Epithelial Stem/Progenitor Cells

Liana Basova; Geraint J Parfitt; Alex Richardson; Vanessa Delcroix; Takeshi Umazume; Daniel Pelaez; David T Tse; Ivo Kalajzic; Nick Di Girolamo; James V Jester; Helen P Makarenkova

doi:10.1016/j.isci.2020.101230

Origin and Lineage Plasticity of Endogenous Lacrimal Gland Epithelial Stem/Progenitor Cells

iScience. 2020 Jun 26;23(6):101230. doi: 10.1016/j.isci.2020.101230. Epub 2020 Jun 2.

Authors

Affiliations

¹ Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
² School of Optometry and Vision Sciences, Cardiff University, Maindy Road, Cardiff CF24 4HQ, UK; European Cancer Stem Cell Research Institute, Cardiff University, Maindy Road, Cardiff CF24 4HQ, UK; The Gavin Herbert Eye Institute, University of California, Irvine, CA 92697, USA.
³ Department of Ophthalmology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
⁴ Department of Ophthalmology/Bascom Palmer Eye Institute, Miami, FL, USA.
⁵ Reconstructive Sciences Center for Regenerative Medicine and Skeletal Development, University of Connecticut (UCONN) Health, Farmington, CT, USA.
⁶ The Gavin Herbert Eye Institute, University of California, Irvine, CA 92697, USA.
⁷ Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: hmakarenk@scripps.edu.

Abstract

The lacrimal gland (LG) is an exocrine organ responsible for the secretion of aqueous tear film. Regenerative and stem cell therapies that target LG repair are coming to the fore, although our understanding of LG cell lineage hierarchy is still incomplete. We utilize the analysis of label-retaining cells (LRCs) and genetic lineage tracing to define LG cell lineage hierarchy. Our study suggests that embryonic LG contains unique long-lived multipotent stem cells that give rise to all postnatal epithelial cell types. Following birth, lineages become established and the fate of progenitor cell descendants becomes restricted. However, some cell lineages retain plasticity after maturation and can trans-differentiate into other cell types upon injury. The demonstration that the LG contains progenitor cells with different levels of plasticity has profound implications for our understanding of LG gland function in homeostasis and disease and will be helpful for developing stem cell-based therapies in the future.

Keywords: Biological Sciences; Cell Biology; Developmental Biology; Stem Cells Research.

Abstract

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