Reconstitution of Pluripotency from Mouse Fibroblast through Sall4 Overexpression

Abstract

Somatic cells can be reprogrammed into pluripotent stem cells (iPSCs) by overexpressing de-fined transcription factors. Specifically, OCT4 single factor overexpression has been shown to reprogram mouse fibroblasts into iPSCs. Yet, whether other single factor can induce iPSCs from fibroblasts remains unknown. Here, we demonstrate that, under an optimized reprogram-ming medium iCD4, SALL4 alone is capable to reprogram mouse fibroblast into iPSCs. Mech-anistically, SALL4 inhibits somatic genes and activates pluripotent genes (Rsk1, Esrrb and Tfap2c) to facilitate reprogramming. Furthermore, we show that co-overexpressing SALL4 and OCT4 enhances reprogramming efficiency synergistically. In detail, SALL4-activated Rsk1/Esrrb/Tfap2c, OCT4-activated Sox2, SALL4-suppressed Nkx6.1, and OCT4-suppressed Sbsn cooperate to facilitate SALL4/OCT4-mediated reprogramming. Overall, our study estab-lishes an efficient method for iPSCs induction using SALL4 single factor, and provides in-sights into the synergistic effects of SALL4 and OCT4 during somatic cell reprogramming.