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

Abstract During development, human primordial germ cells (hPGCs) transition through a transcriptional and epigenetic state similar to pre-implantation naive ground state epiblast cells. In hPGCs, this state is called naive-like ground state pluripotency. Diagnostic transcription factors that define this state include TFAP2C, KLF4, and TFCP2L1, with TFAP2C necessary for both establishment of the naive-like ground state in hPGC-like cells (hPGCLCs) and establishment of naive ground state human embryonic stem cells (hESCs). Here, we show that KLF4 and TFCP2L1 are not required for hPGC specification or establishment of the naive-like ground state in hPGCLCs. Instead, KLF4 and TFCP2L1 are each required for reversion of primed hESCs to the self-renewing naive ground state. Additionally, TFCP2L1 but not KLF4 function after hPGC specification in the proliferation and survival of hPGCLCs.