Pluripotent Stem Cells in Reproductive Medicine: Formation of the Human Germ Line in Vitro

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Abstract

The germ cell lineage and germ line inheritance have fascinated ­biologists for centuries. Clinically, the function of germ cells in sexually reproducing organisms is to ensure reproductive fitness and to guard against extinction. However, the consequence of abnormal germ cell development can lead to devastating outcomes, including germ cell tumors, spontaneous recurrent miscarriage, fetal demise, infant morbidity and mortality, and birth defects. To overcome abnormal germ cell development, it has been proposed that germ cells could be generated from pluripotent stem cells in vitro. The technology for creating germ cells in this manner remains theoretical. However, recent advances suggest that the field is progressing toward this goal. In particular, the identification, isolation, and characterization of the initial step in human germ cell development has recently been reported by multiple groups. Furthermore, the birth of live, healthy, fertile young has now been achieved following fertilization of murine in vitro–derived germ cells. This remarkable achievement in the mouse has stemmed from years of studies aimed at understanding the first step in murine germ cell development, the formation of primordial germ cells (PGCs). This chapter describes the events in human PGC development in vivo and how this information should instruct PGC differentiation from human pluripotent stem cells in vitro.