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

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Stem Cell Biology

Background:

• The lacrimal gland (LG) produces the aqueous tear film, essential for ocular surface health.
• Understanding LG cell hierarchy is vital for developing effective regenerative therapies.
• Current knowledge of LG stem cell populations and their lineage potential is limited.

Purpose of the Study:

• To define the cell lineage hierarchy of the lacrimal gland.
• To identify long-lived stem cells and progenitor cells within the LG.
• To investigate the plasticity of LG cell lineages during development and after injury.

Main Methods:

• Label-retaining cell (LRC) analysis to identify quiescent, long-lived cells.
• Genetic lineage tracing to track cell fate and differentiation pathways.
• Comparative analysis of embryonic and postnatal LG development.

Main Results:

• Embryonic LG harbors multipotent stem cells that differentiate into all postnatal epithelial cell types.
• Postnatal LG lineages become restricted, but progenitor cells retain plasticity.
• Injury can induce trans-differentiation in mature LG cell lineages.

Conclusions:

• The lacrimal gland possesses a distinct cell lineage hierarchy with early multipotent stem cells.
• Mature LG cells exhibit plasticity, offering potential for therapeutic interventions.
• Findings provide a foundation for developing targeted stem cell-based therapies for LG disorders.