Chicken Interspecies Chimerism Unveils Human Pluripotency

Human pluripotent stem cells (hPSCs) are commonly kept in a primed state but also able to acquire a more immature naive state under specific conditions in vitro. Acquisition of naive state changes several properties of hPSCs and might affect their contribution to embryonic development in vivo. However, the lack of an appropriate animal test system has made it difficult to assess potential differences for chimera formation between naive and primed hPSCs. Here, we report that the developing chicken embryo is a permissive host for hPSCs, allowing analysis of the pluripotency potential of hPSCs. Transplantation of naive-like and primed hPSCs at matched developmental stages resulted in robust chimerism. Importantly, the ability of naive-like but not of primed hPSCs to form chimera was substantially reduced when injected at non-matched developmental stages. We propose that contribution to chick embryogenesis is an informative and versatile test to identify different pluripotent states of hPSCs.

Automated summary

The developing chicken embryo is found to be a permissive host for analyzing the pluripotency potential of hPSCs. Both naive-like and primed hPSCs can form robust chimerism when transplanted at matched developmental stages, but only naive-like hPSCs show reduced ability to form chimera when injected at non-matched developmental stages. Conclusively, contribution to chick embryogenesis serves as an informative and versatile test to identify different pluripotent states of hPSCs.