Generation of rat lungs by blastocyst complementation in Fgfr2b-deficient mouse model
Generation of rat lungs by blastocyst complementation in Fgfr2b-deficient mouse model
复制标题
Fgfr2b 缺陷小鼠模型中通过囊胚互补产生大鼠肺
DOI：
10.1101/2022.01.05.475149
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Ayako Isotani
中科院分区：
文献类型：
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作者：
Shunsuke Yuri;Yuki Murase;Ayako Isotani
再生医学是弥补移植肺短缺的一种工具，但由于复杂的三维结构和多种细胞类型，在体外构建肺仍然很困难。使用种间嵌合动物的囊胚互补方法作为在动物中创建复杂器官的一种方法已经引起了人们的关注，但尚未实现成功的肺形成。在这里，我们应用“反向囊胚互补法”来阐明在 Fgfr2b 缺陷小鼠模型中形成肺所需的条件。然后，我们通过应用基于四倍体的器官互补方法，在小鼠模型中成功形成了大鼠来源的肺，而无需生成小鼠系。重要的是，即使在小鼠体内，大鼠肺上皮细胞也保留了其发育时间。这一结果提供了关于需要克服物种特异性发育时间障碍以在种间嵌合体中产生功能性肺的有用见解。
Regenerative medicine is a tool to compensate for the shortage of lungs for transplantation, but it remains difficult to construct a lungin vitrodue to the complex three-dimensional structures and multiple cell types required. A blastocyst complementation method using interspecies chimeric animals has been attracting attention as a way to create complex organs in animals, but successful lung formation has not yet been achieved. Here, we applied a “reverse-blastocyst complementation method” to clarify the conditions required to form lungs in an Fgfr2b-deficient mouse model. We then successfully formed a rat-derived lung in the mouse model without generating a mouse line by applying a tetraploid-based organ-complementation method. Importantly, rat lung epithelial cells retained their developmental timing even in the mouse body. This result provides useful insights regarding the need to overcome the barrier of species-specific developmental timing in order to generate functional lungs in interspecies chimeras.