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
Affiliations
Liana Basova
Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Geraint J. Parfitt
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
Alex Richardson
Department of Ophthalmology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
Vanessa Delcroix
Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Takeshi Umazume
Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Daniel Pelaez
Department of Ophthalmology/Bascom Palmer Eye Institute, Miami, FL, USA
David T. Tse
Department of Ophthalmology/Bascom Palmer Eye Institute, Miami, FL, USA
Ivo Kalajzic
Reconstructive Sciences Center for Regenerative Medicine and Skeletal Development, University of Connecticut (UCONN) Health, Farmington, CT, USA
Nick Di Girolamo
Department of Ophthalmology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
James V. Jester
The Gavin Herbert Eye Institute, University of California, Irvine, CA 92697, USA
Helen P. Makarenkova
Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA; Corresponding author
Summary: 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.
