Generation of rat-derived lung epithelial cells in Fgfr2b-deficient mice retains species-specific development.

Regenerative medicine is a tool to compensate for the shortage of lungs for transplantation, but it remains difficult to construct a lung in vitro due 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, although successful lung formation using interspecies chimeric animals has not yet been achieved. Here, we applied a reverse-blastocyst complementation method to clarify the conditions required to form lungs in an Fgfr2bdeficient mouse model. We then successfully formed a rat-derived lung in the mouse model by applying a tetraploid-based organcomplementation method. Importantly, rat lung epithelial cells retained their developmental timing even in the mouse body. These findings provide useful insights to overcome the barrier of speciesspecific developmental timing to generate functional lungs in interspecies chimeras. [ABSTRACT FROM AUTHOR]