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. 2022 Mar 17;28(3):313–345. doi: 10.1093/humupd/dmac002

Figure 2.

Figure 2.

The core transcriptional network in human pluripotent stem cells and primordial germ cells. Arrows with pointed tips represent activation, and arrows with vertical line tips represent inhibition. In pluripotent stem cells, FGF2, WNT and ACTIVIN signaling pathways are essential to activate the gene expression program for pluripotency. In response to the signals, OCT4, SOX2 and NANOG are activated and form a core transcriptional network that suppresses the somatic and germline gene expression program. Once human pluripotent stem cells (hPSCs) start to differentiate toward germline, WNT3, ACTIVIN and BMP4 signals activate EOMES and GATA3, which then activate the expression of a few transcription factors essential for germ cell development, including SOX17, TFPAP2C and PRDM1. Moderate expression of pluripotency transcription factor OCT4 is also critical for human germ cell development. Upon differentiation, the expression of OCT4 is gradually reduced, and the expression of its functional partner in hPSCs, SOX2, is diminished. Instead, OCT4 partners with PAX5 in human primordial germ cells (hPGCs) to activate the expression of PRDM1.