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Embryonic stem (ES) cells share markers with undifferentiated primordial germ cells (PGCs). Here, we discovered that a cellular state with some molecular markers of male gonocyte induction, including a G1/S phase arrest and upregulation of specific genes such as  Nanos2 ,  Tdrd1 ,  Ddx4 ,  Zbtb16  and  Plk1s1 , can be chemically induced in male mouse ES cells  in vitro , which we termed gonogenic stimulated transition (GoST). After longer culture of the resulting GoST cells without chemical stimulation, several molecular markers typical for early gonocytes were detected including the early gonocyte marker Tex101. Motivated by previous studies that found multipotency in cell lines derived from neonatal male germ cells  in vitro , we then compared the differentiation potential of GoST cells to that of ES cells  in vitro . Interestingly, GoST cells showed equal neurogenic, but enhanced cardiogenic and hepatogenic differentiation compared to ES cells  in vitro . This work shows for the first time that some important molecular markers of the first developmental sexual differentiation program can be induced in male mouse ES cells  in vitro  and defines a novel concept to generate cells with enhanced multipotency.

A gonogenic stimulated transition of mouse embryonic stem cells with enhanced control of diverse differentiation pathways