Depicting early human development and germ cell origin with porcine embryos

Human primordial germ cells (hPGCs), the precursors of sperm and eggs, originate in early postimplantation embryos. Since early human embryos cannot be investigated directly, we extended our recent in vitro model for hPGC fate, alongside direct analysis of early porcine embryos, which develop in a highly similar manner. Here we show that porcine PGCs (pPGCs) originate from the posterior pre-primitive streak epiblast in response to WNT and BMP-pSMAD signalling, followed by sequential induction of SOX17–BLIMP1 expression. This is reminiscent of our observations for the human in vitro counterpart. Mechanistic analysis in the culture model for hPGC specification and gastrulation shows that a balanced SOX17-BLIMP1 gene dosage is critical and sufficient for PGC specification; SOX17 subsequently induces definitive endoderm during gastrulation. We demonstrate that porcine embryos when combined with a tractable human model system can provide insights on early human development and mechanisms of early cell fate decisions. Overall design: RNA-Seq analysis to investigate transcriptomes of hESCs and hPGCs induced from hESCs with cytokines or with overexpression of SOX17 and BLIMP1