Mammalian Germ Cell Development: From Mechanism to In Vitro Reconstitution

Abstract

The germ cell lineage gives rise to totipotency and perpetuates and diversifies genetic as well as epigenetic information. Specifically, germ cells undergo epigenetic reprogramming/programming, replicate genetic information with high fidelity, and create genetic diversity through meiotic recombination. Driven by advances in our understanding of the mechanisms underlying germ cell development and stem cell/reproductive technologies, research over the past 2 decades has culminated in the in vitro reconstitution of mammalian germ cell development: mouse pluripotent stem cells (PSCs) can now be induced into primordial germ cell-like cells (PGCLCs) and then differentiated into fully functional oocytes and spermatogonia, and human PSCs can be induced into PGCLCs and into early oocytes and prospermatogonia with epigenetic reprogramming. Here, I provide my perspective on the key investigations that have led to the in vitro reconstitution of mammalian germ cell development, which will be instrumental in exploring salient themes in germ cell biology and, with further refinements/extensions, in developing innovative medical applications.

Keywords: embryonic stem cells; epigenetic reprogramming; germ cells; human; induced pluripotent stem cells; mouse; primordial germ cell-like cells; specification.

Mitinori Saitou received his MD from the Kyoto University Faculty of Medicine in 1995 and received his PhD in 1999 for his study of the structure and function of tight junctions under Professor Shoichiro Tsukita in the Kyoto University Graduate School of Medicine. He then moved to the Wellcome Trust/Cancer Research UK Gurdon Institute, where he worked as a postdoctoral research associate in Professor Azim Surani's laboratory, focusing on the origin of the germ line in the mouse. He was appointed team leader at the RIKEN Center for Developmental Biology in 2003. He was appointed professor at the Kyoto University Graduate School of Medicine in 2009. He was appointed director of the JST ERATO program in 2011. He was appointed professor at the Kyoto University Institute for Advanced Study and director of the Institute for the Advanced Study of Human Biology in 2018. His laboratory has clarified the mechanism of germ cell specification in mice and has established a foundation for in vitro gametogenesis research in mice, non-human primates, and humans. Mitinori Saitou has received several awards, such as the Takeda Prize for Medicine, the Academic Award of the Mochida Memorial Foundation, the Asahi Prize, the Uehara Prize, the Imperial Prize and Japan Academy Prize, and the ISSCR 2020 Momentum Award. He is an associate member of the European Molecular Biology Organisation.