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

EMBO Molecular Medicine

卷:10

William R Ryan¹  Jolie L Chang¹  Aaron D Tward¹  Alison J May²  Sarah M Knox²  Noel Cruz‐Pacheco²  Sara Nathan²  Elaine Emmerson²  Aaron J Mattingly²  Lionel Berthoin² 

[1] Department of Otolaryngology University of California San Francisco CA USA;

[2] Program in Craniofacial Biology Department of Cell and Tissue Biology University of California San Francisco CA USA;

关键词: radiotherapy;    regeneration;    salivary gland;    SOX2;    stem cells;   

DOI  :  10.15252/emmm.201708051

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown