Fig. 4.

Regulatory pathways and epigenetic modifications related to germline specification. A Regulatory pathways for PGC specification in mice. The BMP4 signaling pathway directly or indirectly activates the WNT signaling pathway, which activates T cells. T cells directly activate Blimp1 and Prdm14. Tcfap2c is a downstream target of Blimp1, enabling PGCs to maintain Blimp1 activity. Prdm14 activates Tfap2C, which enhances the activity of Blimp1, while the expression of Blimp1 activates the expression of Tfap2C. Otx2 functions repressively upstream of PGC transcription factors and is inhibited by the BMP4 and WNT signaling pathways. B Regulatory pathways for PGC specification in humans. The mechanism underlying hPGC specification was distinct from that of mPGC specification. Sox17 plays an important role in hPGC specification. The BMP4 signaling pathway initially activates Sox17, whereas WNT activates Eomes, which further activates Sox17. Sox17 is upstream of Blimp1 in the PGC specification circuit. Blimp1 can be upregulated by Tfap2C, which is upregulated by Sox17 in response to the BMP4 signal. C Epigenetic modifications during the induction from ESCs to PGCLCs in mice and humans