KLF17 promotes human naïve pluripotency but is not required for its establishment

Rebecca A Lea, Afshan McCarthy, Stefan Boeing, Todd Fallesen, Kay Elder, Phil Snell, Leila Christie, Sarah Adkins, Valerie Shaikly, Mohamed Taranissi, Kathy K Niakan
2021
Current knowledge of the transcriptional regulation of human pluripotency is incomplete, with lack of inter-species conservation observed. Single-cell transcriptomics analysis of human embryos previously enabled us to identify transcription factors, including the zinc-finger protein KLF17, that are enriched in the human epiblast and naïve hESCs. Here we show that KLF17 is expressed coincident with the known pluripotency-associated factors NANOG and SOX2 across human blastocyst development. We
more » ... vestigate the function of KLF17 using primed and naïve hESCs for gain- and loss-of-function analyses. We find that ectopic expression of KLF17 in primed hESCs is sufficient to induce a naïve-like transcriptome and that KLF17 can drive transgene-mediated resetting to naïve pluripotency. This implies a role for KLF17 in establishing naïve pluripotency. However, CRISPR-Cas9-mediated knockout studies reveal that KLF17 is not required for naïve pluripotency acquisition in vitro. Transcriptome analysis of naïve hESCs identifies subtle effects on metabolism and signalling pathways following KLF17 loss-of-function, and possible redundancy with other KLF paralogues. Overall, we show that KLF17 is sufficient, but not necessary, for naïve pluripotency under the given in vitro conditions.
doi:10.25418/crick.17143883 fatcat:4zoaljvryrfwpflnydikstt2nm