Salivary glands regenerate after radiation injury through SOX2-mediated secretory cell replacement

Elaine Emmerson, Alison J May, Lionel Berthoin, Noel Cruz-Pacheco, Sara Nathan, Aaron J Mattingly, Jolie L Chang, William R Ryan, Aaron D Tward, Sarah M Knox

Research output: Contribution to journalArticlepeer-review

Abstract

Salivary gland acinar cells are routinely destroyed during radiation treatment for head and neck cancer that results in a lifetime of hyposalivation and co‐morbidities. A potential regenerative strategy for replacing injured tissue is the reactivation of endogenous stem cells by targeted therapeutics. However, the identity of these cells, whether they are capable of regenerating the tissue, and the mechanisms by which they are regulated are unknown. Using in vivo and ex vivo models, in combination with genetic lineage tracing and human tissue, we discover a SOX2+ stem cell population essential to acinar cell maintenance that is capable of replenishing acini after radiation. Furthermore, we show that acinar cell replacement is nerve dependent and that addition of a muscarinic mimetic is sufficient to drive regeneration. Moreover, we show that SOX2 is diminished in irradiated human salivary gland, along with parasympathetic nerves, suggesting that tissue degeneration is due to loss of progenitors and their regulators. Thus, we establish a new paradigm that salivary glands can regenerate after genotoxic shock and do so through a SOX2 nerve‐dependent mechanism.

Original languageEnglish
Article numbere8051
Number of pages18
JournalEMBO Molecular Medicine
Volume10
Issue number3
Early online date15 Jan 2018
DOIs
Publication statusPublished - 1 Mar 2018

Keywords

  • Journal Article

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