Divergent Roles for KLF4 and TFCP2L1 in Naive Ground State Pluripotency and Human Primordial Germ Cell Development.

During embryo development, human primordial germ cells (hPGCs) express a naive gene expression program with similarities to pre-implantation naive epiblast (EPI) cells and naive human embryonic stem cells (hESCs). Previous studies have shown that TFAP2C is required for establishing naive gene expression in these cell types, however the role of additional naive transcription factors in hPGC biology is not known. Here, we show that unlike TFAP2C, the naive transcription factors KLF4 and TFCP2L1 are not required for induction of hPGC-like cells (hPGCLCs) from hESCs, and they have no role in establishing and maintaining a naive-like gene expression program in hPGCLCs with extended time in culture. Taken together, our results suggest a model whereby the molecular mechanisms that drive naive gene expression in hPGCs/hPGCLCs are distinct from those in the naive EPI/hESCs.