Diverse progenitor cells preserve salivary gland ductal architecture after radiation-induced damage
Diverse progenitor cells preserve salivary gland ductal architecture after radiation-induced damage
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DOI：
10.1242/dev.166363
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发表时间：
2018-11-01
期刊：
影响因子：
4.6
通讯作者：
Knox, Sarah M.
中科院分区：
文献类型：
--
作者：
May, Alison J.;Cruz-Pacheco, Noel;Knox, Sarah M.
长期以来，人们一直认为唾液腺的导管系统对放射性损伤具有抵抗力，放射性损伤是头颈部癌症患者接受放射治疗时常见的副作用。然而，导管是否能够再生后，遗传毒性损伤，或是否损害导管细胞诱导谱系可塑性，已在其他器官系统中报道，仍然是未知的。在这里，使用小鼠唾液腺，我们表明，两个导管祖细胞群体，专门标记的KRT 14和KIT，保持nono-verlapping导管隔室辐射暴露后，但这样做通过不同的细胞机制。KRT 14（+）祖细胞是快速循环细胞，其以持续的方式响应辐射诱导的损伤而增殖，并且不对称地分裂以产生较大颗粒导管的分化细胞。相反，KIT+闰管细胞是闰管的长寿祖细胞，在稳态期间或γ辐射后经历很少的细胞分裂，从而以缓慢的细胞更新速率维持导管结构。总之，这些数据说明了唾液腺导管的再生能力，并强调了唾液祖细胞用于维持组织结构的损伤反应的异质性。
The ductal system of the salivary gland has long been postulated to be resistant to radiation-induced damage, a common side effect incurred by head and neck cancer patients receiving radiotherapy. Yet, whether the ducts are capable of regenerating after genotoxic injury, or whether damage to ductal cells induces lineage plasticity, as has been reported in other organ systems, remains unknown. Here, using the murine salivary gland, we show that two ductal progenitor populations, marked exclusively by KRT14 and KIT, maintain nono-verlapping ductal compartments after radiation exposure but do so through distinct cellular mechanisms. KRT14(+) progenitor cells are fast-cycling cells that proliferate in response to radiation-induced damage in a sustained manner and divide asymmetrically to produce differentiated cells of the larger granulated ducts. Conversely, KIT+ intercalated duct cells are long-lived progenitors for the intercalated ducts that undergo few cell divisions either during homeostasis or after gamma radiation, thus maintaining ductal architecture with slow rates of cell turnover. Together, these data illustrate the regenerative capacity of the salivary ducts and highlight the heterogeneity in the damage responses used by salivary progenitor cells to maintain tissue architecture.