Induced Pluripotency in Chicken Embryonic Fibroblast Results in a Germ Cell Fate
Germ cells are critically important as the vehicle that passes genetic information from one generation to the next. Despite the importance of these cells, little is known about the mechanisms underlying the acquisition and maintenance of germ cell character. In this study by using a reprogramming strategy, we demonstrate the generation of chicken induced PGCs (ciPGCs) by over expression of human transcription factors in embryonic fibroblast. These ciPGCs express pluripotent markers POU5F1, SSEA1 and the germ cell defining proteins CVH and DZAL, closely resembling in vivo source PGCs instead of embryonic stem cells (ESCs). Moreover, these CXCR4 expressing ciPGCs were capable of migrating to the embryonic gonad after injection into the vasculature of stage 15 embryos, indicating the acquisition of a germ cell fate in these cells.
The capability to derive germ cell from somatic cell lines would significantly facilitate the research on germ cell specification and development in avian species, as these events happen before the egg is laid and it is challenging to study by using in vivo PGCs. Availability of ciPGCs in vitro would also facilitate the study of the toxins that affecting the germ cell development using the avian model, since after exposure to toxins the germ cells could be easily re-introduced to the chicken embryo and events as migration could be evaluated in an in vivo context, while such experiment is hard in mammalian model and impossible in human.
Endangered bird conservation is another potential application of ciPGCs. Over 1300 avian species, or 13% of the total population, are threatened by extinction. A recent report revealed that functional gametes could be produced from interspecies transplantation of PGCs, suggesting a new strategy for conservation of endangered birds by using domestic host. However, this process still requires the sacrifice of endangered embryos for the collection of PGCs. Direct derivation of iPGCs from somatic cells (feather pulp, post-hatched egg shells) would circumvent the sacrifice of embryos for PGCs isolation and facilitate the implementation of this strategy. Moreover, it provide a potential strategy to bring back and repopulate the extinct birds from the frozen cell samples as stored in San Diego’s Frozne Zoo and the cell banks around the world.