Chicken Interspecies Chimerism Unveils Human Pluripotency

Abstract

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.

Avian Embryonic Culture: A Perspective of In Ovo to Ex Ovo and In Vitro Studies

“…This suggests that the pluripotency mechanism in different avian species is diverse at the early stage of freshly laid eggs and cannot be relied only on a chick model. A recent study of in ovo interspecies chimerism also shows the striking result to highlight the pluripotent state at equivalent points between human versus chick at an early embryonic development in that the EGK X blastodermal cells matched well with naïve human pluripotent stem cells (hPSCs), while the primed hPSCs can incorporate into the gastrulating epiblasts of chick embryos ( Akhlaghpour et al, 2021 ) ( Figure 1 ). In addition, CAM is used to understand pluripotency properties in an interspecies manner.…”

“…In ovo culture depicts the early stages (EGK X to HH28, day 0–5) of avian embryos using a chick as a model. The early embryonic stage of a chick embryo at the freshly laid egg and stage HH4 can be incorporated well with naive and primed ESCs, respectively ( Akhlaghpour et al, 2021 ). Dark magenta dots in the embryo stages HH14–19 and HH25–28 represent primordial germ cells (PGCs) circulating in blood vessels and migrating to the genital ridges which later become gonads ( Nakamura et al, 2013 ).…”

In Vivo Generation of Organs by Blastocyst Complementation: Advances and Challenges

“…The fact that humans and pigs are in many respects more similar than humans and mice, suggests that the xenobarrier between the two former species may prove easier to cross. Nevertheless, such an interspecies barrier does exist and this is why active research is currently being conducted between different species in order to elucidate its mechanisms and propose possible strategies to overcome it ( 68 - 71 ). Interestingly, it was recently reported that deletion of insulin-like growth factor 1 receptor (Igf1r) in mouse blastocysts significantly facilitates their colonization by both mouse and rat donor cells resulting in highly chimeric animals ( 72 ).…”

Kidney ECM Pregel Nanoarchitectonics for Microarrays to Accelerate Harvesting Gene-Edited Porcine Primary Monoclonal Spheres

“…The quality of the cells will directly affect the development of recombinant embryos in the later stage, so it is the key and prerequisite for the production of gene-edited pigs. 7 …”

“…In the process of SCNT, obtaining gene-edited nuclear donor cells in good condition is an important step in the preparation of gene-edited pigs. The quality of the cells will directly affect the development of recombinant embryos in the later stage, so it is the key and prerequisite for the production of gene-edited pigs …”