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Although stem cell aging leads to a decline in tissue homeostasis and regenerative capacity, it remains unclear whether salivary gland stem cell function changes during this process. However, the salivary glands are gradually replaced by connective tissue during aging. Here, we show a decline in the stem cell ability of CD133-positive stem/progenitor cells in the salivary glands of aged mice. The CD133-positive cells were isolated from young, adult, and aged mice. The number of CD133-positive cells was significantly decreased in aged mice. They also showed a lower sphere formation capacity compared to young and adult mice. RNA sequencing revealed that CD133-positive cells in aged mice exhibited lower gene expression of several aging-related genes, including FoxO3a, than those in young and adult mice. Salivary gland cells infected with a recombinant lentivirus encoding the FoxO3a gene showed a reduction in oxidative stress induced by hydrogen peroxide compared with those infected with a control virus. Thus, FoxO3a may inhibit stem cell aging via oxidative stress., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Exocrine glands share a common morphology consisting of ductal, acinar, and basal/myoepithelial cells, but their functions and mechanisms of homeostasis differ among tissues. Salivary glands are an example of exocrine glands, and they have been reported to contain multipotent stem cells that differentiate into other tissues. In this study, we purified the salivary gland stem/progenitor cells of adult mouse salivary glands using the cell surface marker CD133 by flow cytometry. CD133 + cells possessed stem cell capacity, and the transplantation of CD133 + cells into the submandibular gland reconstituted gland structures, including functional acinar. CD133 + cells were sparsely distributed in the intercalated and exocrine ducts and expressed Sox9 at higher levels than CD133 - cells. Moreover, we demonstrated that Sox9 was required for the stem cell properties CD133 + cells, including colony and sphere formation. Thus, the Sox9-related signaling may control the regeneration salivary glands., (Copyright © 2019 Elsevier Inc. All rights reserved.)