Steps toward the generation of ovarian somatic cells from pluripotent stem cells

Abstract

The generation of functional gametes, both eggs and sperm, from murine pluripotent stem cell (PSC) sources, has set the stage for the eventual use of this emerging technology in other species. With the field enthusiastically embracing this eventuality, in particular for animal conservation efforts, there are a number of key factors to consider regarding the applicability of these methods across species, particularly with regard to the generation of eggs. To date, published studies point to the need for fetal somatic tissue and primitive granulosa cells to serve as a niche for the growth and maturation of oocytes generated from PSCs. In practice, the need for such tissue represents a major limitation when attempting to apply this to species in which access to fetal ovaries is limited or unethical. To circumvent this, we and others have derived methods to generate ovarian granulosa cells from PSCs, albeit with low yield. Herein we present an update on the status of generating early stage granulosa cells from PSCs, and provide evidence for improvements based on a stepwise, 2-dimensional protocol for the directed differentiation of human PSCs.