Open AccessDiverse epithelial cell populations contribute to regeneration of secretory units in injured salivary glands
Author(s) -
Ninche Ninche,
Mingyu Kwak,
Soosan Ghazizadeh
Publication year - 2020
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.192807
Subject(s) - myoepithelial cell , biology , ductal cells , regeneration (biology) , progenitor cell , microbiology and biotechnology , salivary gland , stem cell , acinar cell , cellular differentiation , epithelium , immunology , endocrinology , pancreas , immunohistochemistry , biochemistry , genetics , gene
Salivary glands exert exocrine secretory function to provide saliva for lubrication and protection of the oral cavity. Its epithelium consists of several differentiated cell types including acinar, ductal and myoepithelial cells that are maintained in a lineage-restricted manner during homeostasis or after mild injuries. Glandular regeneration following a near complete loss of secretory cells, however, may involve cellular plasticity, although the mechanism and extent of such plasticity remain unclear. Here, by combining lineage-tracing experiments with a model of severe glandular injury in the mouse submandibular gland, we show that de novo formation of acini involves induction of cellular plasticity in multiple non-acinar cell populations. Fate-mapping analysis revealed that although ductal stem cells marked by cytokeratin K14 and Axin2 undergo a multipotency switch, they do not make a significant contribution to acinar regeneration. Intriguingly, more than 80% of regenerated acini derive from differentiated cells including myoepithelial and ductal cells that appear to dedifferentiate to a progenitor-like state before re-differentiation to acinar cells. The potential of diverse cell populations serving as a reserve source for acini widens the therapeutic options for hyposalivation.