Naive-like pluripotency to pave the way for saving the northern white rhinoceros from extinction

The northern white rhinoceros (NWR) is probably the earth's most endangered mammal. To rescue the functionally extinct species, we aim to employ induced pluripotent stem cells (iPSCs) to generate gametes and subsequently embryos in vitro. To elucidate the regulation of pluripotency and differentiation of NWR PSCs, we generated iPSCs from a deceased NWR female using episomal reprogramming, and observed surprising similarities to human PSCs. NWR iPSCs exhibit a broad differentiation potency into the three germ layers and trophoblast, and acquire a naive-like state of pluripotency, which is pivotal to differentiate PSCs into primordial germ cells (PGCs). Naive culturing conditions induced a similar expression profile of pluripotency related genes in NWR iPSCs and human ESCs. Furthermore, naive-like NWR iPSCs displayed increased expression of naive and PGC marker genes, and a higher integration propensity into developing mouse embryos. As the conversion process was aided by ectopic BCL2 expression, and we observed integration of reprogramming factors, the NWR iPSCs presented here are unsuitable for gamete production. However, the gained insights into the developmental potential of both primed and naive-like NWR iPSCs are fundamental for in future PGC-specification in order to rescue the species from extinction using cryopreserved somatic cells.

Automated summary

This study aims to rescue the critically endangered northern white rhinoceros species by using induced pluripotent stem cells (iPSCs) to generate gametes and embryos in vitro. The study found that NWR iPSCs have similarities to human iPSCs and can differentiate into multiple germ layers and trophoblast. Furthermore, the naive-like state of NWR iPSCs is pivotal for differentiation into primordial germ cells (PGCs).