The female germline undergoes a unique sequence of differentiation processes that endows totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here, we report successful reconstitution in vitro of the entire process of oogenesis from pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells as well as induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts. Moreover, pluripotent stem cell lines were re-derived from the in vitro-generated eggs, thereby reconstituting a female germline cycle in a dish. This culture system will provide a unique platform for elucidating the molecular mechanisms underlying totipotency and clues to the production of oocytes of other mammalian species in culture.
This study has been published online in Nature on 18th Oct 2016.
Reconstitution of oogenesis using pluripotent stem cells that yields functional eggs has long been sought. In our culture system, fully functional oocytes were produced from pluripotent stem cells including embryonic stem cells and iPS cells from adult tail tip fibroblasts. In the sequence of culture condition (IVDi: in vitro differentiation, IVG: in vitro growth, and IVM: in vitro maturation), pluripotent stem cells differentiated into oogonia, primary oocytes and mature oocytes. The oocytes were fully functional, as they gave rise to healthy pups. The pups grew up to adult mice and they were fertile.