Abstract：
Whole salivary gland generation and transplantation offer potential therapies for salivary gland dysfunction. However, the specific lineage required to engineer complete salivary glands has remained elusive. In this study, we identify the Foxa2 lineage as a critical lineage for salivary gland development through conditional blastocyst complementation (CBC). Foxa2 lineage marking begins at the boundary between the endodermal and ectodermal regions of the oral epithelium before the formation of the primordial salivary gland, thereby labeling the entire gland. Ablation of Fgfr2 within the Foxa2 lineage in mice leads to salivary gland agenesis. We reversed this phenotype by injecting donor pluripotent stem cells into the mouse blastocysts, resulting in mice that survived to adulthood with salivary glands of normal size, comparable to those of their littermate controls. These findings demonstrate that CBC-based salivary gland regeneration serves as a foundational experimental approach for future advanced cell-based therapies.
摘要：
整个唾液腺的产生和移植为唾液腺功能障碍提供了潜在的治疗方法。然而,工程完整唾液腺所需的特定谱系仍然难以捉摸。在这项研究中,我们确定Foxa2谱系是通过条件胚泡互补（CBC）唾液腺发育的关键谱系。Foxa2谱系标记始于原始唾液腺形成之前口腔上皮的内胚层和外胚层区域之间的边界，从而标记整个腺体。在小鼠中Foxa2谱系内的Fgfr2的消融导致唾液腺发育不全。我们通过将供体多能干细胞注射到小鼠胚泡中来逆转这种表型，导致小鼠存活到成年，唾液腺大小正常，与他们同窝的对照组相当。这些发现表明，基于CBC的唾液腺再生可作为未来先进的基于细胞的疗法的基础实验方法。
