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Functional primordial germ cell–like cells from pluripotent stem cells in rats

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The in vitro generation of germ cells from pluripotent stem cells (PSCs) can have a substantial effect on future reproductive medicine and animal breeding. A decade ago, in vitro gametogenesis… Click to show full abstract

The in vitro generation of germ cells from pluripotent stem cells (PSCs) can have a substantial effect on future reproductive medicine and animal breeding. A decade ago, in vitro gametogenesis was established in the mouse. However, induction of primordial germ cell–like cells (PGCLCs) to produce gametes has not been achieved in any other species. Here, we demonstrate the induction of functional PGCLCs from rat PSCs. We show that epiblast-like cells in floating aggregates form rat PGCLCs. The gonadal somatic cells support maturation and epigenetic reprogramming of the PGCLCs. When rat PGCLCs are transplanted into the seminiferous tubules of germline-less rats, functional spermatids—that is, those capable of siring viable offspring—are generated. Insights from our rat model will elucidate conserved and divergent mechanisms essential for the broad applicability of in vitro gametogenesis. Description Generating functional rate gametes In the past decade, methods have been developed to generate germ cells from pluripotent stem cells for studies of development and in vitro gametogenesis. However, offspring from in vitro–derived germ cells has only been achieved in mice. Oikawa et al. extend this work beyond mice to a second rodent species, the rat, a leading animal model for biomedical research with many physiological similarities to humans. A stepwise protocol allows for the production of fetal stage rat germ cells that can produce viable offspring upon maturation in the testis and injection of the sperm into unfertilized oocytes. This system will allow comparative studies and enable broader execution and analysis of in vitro gametogenesis. —BAP In vitro–induced rat primordial germ cells undergo spermatogenesis in vivo, enabling the birth of normal offspring.

Keywords: germ; cells pluripotent; pluripotent stem; germ cells; stem cells; primordial germ

Journal Title: Science
Year Published: 2022

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