University of California / Knox SM*
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.
Emmerson E1, May AJ1, Berthoin L1, Cruz-Pacheco N1, Nathan S1, Mattingly AJ1, Chang JL2, Ryan WR2, Tward AD2, Knox SM3.
Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA.
Department of Otolaryngology, University of California, San Francisco, CA, USA.
Program in Craniofacial Biology, Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA email@example.com.