Tanaka Junichi, Miura Akihiro, Shimamura Yuko, Hwang Youngmin, Shimizu Dai, Kondo Yuri, Sawada Anri, Sarmah Hemanta, Ninish Zurab, Mishima Kenji, Mori Munemasa
bioRxiv. 2023 Nov 15:2023.11.13.566845. doi: 10.1101/2023.11.13.566845.
Various patients suffer from dry mouth due to salivary gland dysfunction. Whole salivary gland generation and transplantation is a potential therapy to resolve this issue. However, the lineage permissible to design the entire salivary gland generation has been enigmatic. Here, we discovered Foxa2 as a lineage critical for generating a salivary gland via conditional blastocyst complementation (CBC). Foxa2 linage, but not Shh nor Pitx2, initiated to label between the boundary region of the endodermal and the ectodermal oral mucosa before primordial salivary gland formation, resulting in marking the entire salivary gland. The salivary gland was agenesis by depleting Fgfr2 under the Foxa2 lineage in the mice. We rescued this phenotype by injecting donor pluripotent stem cells into the mouse blastocysts. Those mice survived until adulthood with normal salivary glands compatible in size compared with littermate controls. These results indicated that CBC-based salivary gland generation is promising for next-generation cell-based therapy.
各种患者因唾液腺功能障碍而患有口干症。全唾液腺生成和移植是解决这一问题的一种潜在疗法。然而，用于设计整个唾液腺生成的谱系一直是个谜。在这里，我们通过条件性囊胚互补（CBC）发现Foxa2是生成唾液腺的关键谱系。在原始唾液腺形成之前，Foxa2谱系而非Shh或Pitx2谱系开始在内胚层和外胚层口腔黏膜的边界区域之间标记，从而标记整个唾液腺。通过在小鼠的Foxa2谱系下耗尽Fgfr2，唾液腺发生发育不全。我们通过将供体多能干细胞注射到小鼠囊胚中来挽救这一表型。与同窝对照相比，那些小鼠存活至成年，其唾液腺大小正常。这些结果表明，基于CBC的唾液腺生成在下一代细胞疗法方面很有前景。
