Mice Cloned From Induced Pluripotent Stem Cells (iPSCs)

Recent advances in cell reprogramming have clearly indicated that differentiated somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) that are fully pluripotent by ectopically expressing the Oct4, Sox2, Klf4and c-Myc transcription factors. As we known, iPSCs have been successfully generated in several other species, including the rhesus monkey, rat, bovine,and pig. Subsequently, the generation of gene knockout or knock-in large animals through the transfer of genetically modified iPSC nuclei into enucleated oocytes has been proposed. This method will potentially circumvent the fact that no bona fide embryonic stem cells (ESCs) are available in large animals for gene targeting.Although a few reports have indicated that somatic cell nuclear transfer (SCNT) can be used to generate gene targeted large animals, site-specific gene targeting in somatic cells has been proven rather inefficient. If the iPSCs created in large animals can be used to generate cloned animals by nuclear transfer method, it will dramatically shorten the experimental time-scale and increase the ease of generating gene targeted large animals. However, it remains unknown whether iPSCs could be used for generating cloned animals through nuclear transfer method. Here, we show the successful production of viable cloned mice from inducible iPSCs through nuclear transfer approach in the experiment, and the efficiency is similar to using ESCs derived via normal fertilization. Furthermore, six iPS-cloned mice survived to adulthood and produced second-generation offspring. These efforts strengthened the possibility of utilizing iPSCs to generate gene modified large animals for pharmaceutical purposes in the future.