Pluripotency is the capacity to generate all somatic cells 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 Krüppel-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 replacing KLF4. Moreover, KLF7 is highly expressed in naive PSCs and its forced expression in conventional hPSCs induces upregulation of naive markers and results in efficient chemical resetting to naive PSCs. KLF7 CRISPRi-mediated silencing, while not affecting maintenance of conventional/primed PSCs, greatly reduces the efficiency of chemical resetting. Our data indicate that KLF7 is a general human pluripotency factor and an inducer of pluripotency.
KLF7 is a general inducer of human pluripotency
Pellegrini, Marco;Martini, PaoloMethodology
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2025-01-01
Abstract
Pluripotency is the capacity to generate all somatic cells 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 Krüppel-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 replacing KLF4. Moreover, KLF7 is highly expressed in naive PSCs and its forced expression in conventional hPSCs induces upregulation of naive markers and results in efficient chemical resetting to naive PSCs. KLF7 CRISPRi-mediated silencing, while not affecting maintenance of conventional/primed PSCs, greatly reduces the efficiency of chemical resetting. Our data indicate that KLF7 is a general human pluripotency factor and an inducer of pluripotency.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
