Ethical and moral issues rule out the use of human induced pluripotent stem cells (iPSCs) in chimera studies that would determine the full extent of their reprogrammed state, instead relying on less rigorous assays such as teratoma formation and differentiated cell types. To date, only mouse iPSC lines are known to be truly pluripotent. However, initial mouse iPSC lines failed to form chimeric offspring, but did generate teratomas and differentiated embryoid bodies, and thus these specific iPSC lines were not completely reprogrammed or truly pluripotent. Therefore, there is a need to address whether the reprogramming factors and process used eventually to generate chimeric mice are universal and sufficient to generate reprogrammed iPSC that contribute to chimeric offspring in additional species. Here we show that porcine mesenchymal stem cells transduced with 6 human reprogramming factors (POU5F1, SOX2, NANOG, KLF4, LIN28, and C-MYC) injected into preimplantation-stage embryos contributed to multiple tissue types spanning all 3 germ layers in 8 of 10 fetuses. The chimerism rate was high, 85.3% or 29 of 34 live offspring were chimeras based on skin and tail biopsies harvested from 2- to 5-day-old pigs. The creation of pluripotent porcine iPSCs capable of generating chimeric offspring introduces numerous opportunities to study the facets significantly affecting cell therapies, genetic engineering, and other aspects of stem cell and developmental biology.
Yubing Liu received a scholarship to come to the U.S. and work on germ cell differentiation and signaling from the Chinese Scientific Council. Yubing is from the Animal Genetics and Reproduction division of the Department of Animal Science and Technology at Guangxi University where he received the prestigious Chinese Scientific Council award. This highly competitive award will allow Yubing to perform cutting edge research to improve germ cell formation from human and animal embryonic and induced pluripotent stem cells through genetic manipulation for the next two years in the lab of Dr. West. Yubing’s interest lies in the generation of transgenic animals, particularly the buffalo. Yubing has worked on the development of novel reporter system, conditional knockouts, systems to produce better livestock and now brings his skills to the United States. We are excited to have you join the team Yubing.