KLF7 is a general inducer of human pluripotency

Pluripotency is the capacity to give rise to all differentiated cells of the body and the germ line and is governed by a self-reinforcing network of transcription factors. The forced expression of only some of these factors enables the reprogramming of somatic cells to pluripotency. In murine cells, several kruppel-like factors (KLFs) have been identified as stabilisers and inducers of pluripotency. Human somatic cells are routinely reprogrammed by expression of KLF4 in combination with OCT4, SOX2 and cMYC (OSKM). An extensive transcriptome analysis revealed, however, that KLF4 is barely expressed in conventional human pluripotent stem cells (PSCs). Here we show that KLF7 is robustly expressed in conventional human PSCs and it allows transcription factor-mediated somatic reprogramming. Moreover, we find that KLF7 is highly expressed in naive PSCs and its forced expression in conventional hPSCs induces upregulation of naive markers and boosts efficiency of chemical resetting to naive PSCs, overall suggesting that KLF7 is a general human pluripotency factor and an inducer of pluripotency. Transcriptional analysis of human fibroblasts reprogrammed to iPSCs with OSKM or OSK7M reprogramming cocktails (samples 1-22) and transcriptional analysis of human iPSC expressing KLF7 or an EMPTY control (KiPS KLF7 and KiPS EMPTY) subjected to chemical resetting to naive PSCs (samples 23-47). Samples analysed for reprogramming: 3 replicates of BJ human fibroblasts (fibroblasts controls), 3 replicates of H9 hESCs (conventional PSCs controls), 4 replicates of OSKM P4 (iPSCs obtained with OSKM reprogramming cocktail and stabilised in colture for 4 passages), 4 replicates of OSKM P7 (iPSCs obtained with OSKM reprogramming cocktail and stabilised in colture for 7 passages), 4 replicates of OSK7M P4 (iPSCs obtained with OSK7M reprogramming cocktail and stabilised in colture for 4 passages), OSK7M P7 (iPSCs obtained with OSK7M reprogramming cocktail and stabilised in colture for 7 passages). Samples analysed for chemical resetting: 3 replicates of HPD00 primed-iPSCs (primed controls), 3 replicates of HPD01 naive-iPSCs (naïve controls), 3 replicates of HPD06 naive-iPSCs (naïve controls), 4 replicates of KiPS EMPTY, 4 replicates of niPSC EMPTY (KiPS EMPTY post-chemical resetting), 4 replicates of KiPS KLF7, 4 replicates of niPSC KLF7 (KiPS KLF7 post-chemical resetting).