# KLF7 is a general inducer of human pluripotency

**Authors:** Mattia Arboit, Irene Zorzan, Eleonora Pensabene, Marco Pellegrini, Federica Bertelli, Giorgia Panebianco, Davide Benvegnù, Giada Rossignoli, Paolo Martini, Gianluca Amadei, Elena Carbognin, Graziano Martello

PMC · DOI: 10.1038/s44319-025-00595-2 · EMBO Reports · 2025-10-15

## TL;DR

The study shows that KLF7 can replace KLF4 in reprogramming human cells to pluripotency and helps reset cells to a naive state.

## Contribution

KLF7 is identified as a novel general inducer of human pluripotency that can replace KLF4 in reprogramming.

## Key findings

- KLF7 is robustly expressed in conventional human pluripotent stem cells and allows somatic reprogramming.
- Forced expression of KLF7 induces upregulation of naive pluripotency markers and enables efficient chemical resetting.
- CRISPRi silencing of KLF7 reduces the efficiency of chemical resetting to naive pluripotency.

## 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.

KLF7 is robustly expressed in conventional human PSCs and allows transcription factor-mediated somatic reprogramming replacing KLF4, and efficient chemical resetting to naïve pluripotency. KLF7 is a general human pluripotency factor and an inducer of pluripotency.

KLF7 is robustly expressed in conventional hPSCs and it allows transcription factor-mediated somatic reprogramming along with OCT4, SOX2 and cMYC.KLF7 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, reduces the efficiency of chemical resetting.

KLF7 is robustly expressed in conventional hPSCs and it allows transcription factor-mediated somatic reprogramming along with OCT4, SOX2 and cMYC.

KLF7 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, reduces the efficiency of chemical resetting.

KLF7 is robustly expressed in conventional human PSCs and allows transcription factor-mediated somatic reprogramming replacing KLF4, and efficient chemical resetting to naïve pluripotency. KLF7 is a general human pluripotency factor and an inducer of pluripotency.

## Linked entities

- **Genes:** KLF7 (KLF transcription factor 7) [NCBI Gene 8609], KLF4 (KLF transcription factor 4) [NCBI Gene 9314], POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460], SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657], MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609]
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** KLF4 (KLF transcription factor 4) [NCBI Gene 9314] {aka EZF, GKLF}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, KLF7 (KLF transcription factor 7) [NCBI Gene 8609] {aka UKLF}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

12 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12635360/full.md

## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12635360/full.md

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Source: https://tomesphere.com/paper/PMC12635360