The static magnetic fields (SMFs) impact on biological systems, induce a variety of biological responses, and have been applied to the clinical treatment of diseases. However, the underlying mechanisms remain largely unclear. In this report, by using human mesenchymal stem cells (MSCs) as a model, we investigated the biological effect of SMFs at a molecular and cellular level. We showed that SMF exposure promotes MSC proliferation and activates the expression of transcriptional factors such as FOS (Fos Proto-Oncogene, AP-1 Transcription Factor Subunit) and EGR1 (Early Growth Response 1). In addition, the expression of signal-transduction proteins p-ERK1/2 and p-JNK oscillate periodically with SMF exposure time. Furthermore, we found that the inhibition of the T-type calcium ion channels negates the biological effects of SMFs on MSCs. Together, we revealed that the SMFs regulate T-type calcium ion channels and mediate MSC proliferation via the MAPK signaling pathways.

Somatic cells can be reprogrammed into pluripotent stem cells (iPSCs) by overexpressing defined transcription factors. Specifically, overexpression of OCT4 alone has been demonstrated to reprogram mouse fibroblasts into iPSCs. However, it remains unclear whether any other single factor can induce iPSCs formation. Here, we report that SALL4 alone, under an optimized reprogramming medium iCD4, is capable of reprogramming mouse fibroblasts into iPSCs. Mechanistically, SALL4 facilitates reprogramming by inhibiting somatic genes and activating pluripotent genes, such as Esrrb and Tfap2c. Furthermore, we demonstrate that co-overexpressing SALL4 and OCT4 synergistically enhances reprogramming efficiency. Specifically, the activation of Rsk1/Esrrb/Tfap2c by SALL4, alongside OCT4’s activation of Sox2 and the suppression of Mndal by SALL4 and Sbsn by OCT4, cooperate to facilitate SALL4+OCT4-mediated reprogramming. Overall, our study not only establishes an efficient method for iPSCs induction using the SALL4 single factor but also provides insights into the synergistic effects of SALL4 and OCT4 in reprogramming.

Background: Thymidine analogs have long been recognized for their ability to randomly incorporate into DNA. However, the precise mechanisms through which thymidine analogs facilitate cell fate transition remains unclear. Results: Here, we discovered a strong correlation between the dosage dependence of thymidine analogs and their ability to overcome reprogramming barrier. The extraembryonic endoderm (XEN) state seems to be a cell's selective response to DNA damage repair (DDR), offering a shortcut to overcome reprogramming barriers. Meanwhile, we found that homologous recombination repair (HRR) pathway causes an overall epigenetic reshaping of cells and enabling them to overcome greater barriers. This response leads to the creation of a hypomethylated environment, which facilitates the transition of cell fate in various reprogramming systems. We term this mechanism as Epigenetic Reshaping through Damage (ERD). Conclusion: Overall, our study finds that BrdU/IdU can activate the DNA damage repair pathway (HRR), leading to increased histone acetylation and genome-wide DNA demethylation, regulating somatic cell reprogramming. This offers valuable insights into mechanisms underlying cell fate transition. Graphical

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.

Rebuilding human naïve pluripotency from primed stem cells is essential for generating pre-implantation epiblast-like cells, a key source for regenerative medicine. Here we present a defined, feeder-free protocol that efficiently converts primed human pluripotent stem cells (hPSCs) to a naïve-like state within 12 days. Integrated ATAC-seq, RNA-seq and miRNA-seq analyses reveal a rapid chromatin rewiring marked by increased accessibility at OCT/KLF motifs, closure at ZIC/RFX/NFκB sites, upregulation of miR-372/373 and miR-182/183, and downregulation of miR-302 and miR-363/106 clusters. Functional assays demonstrate that the inflammatory transcription factor NFκB/RELA blocks naïve induction by activating peri-implantation barrier genes, including IKBKE and VEGFR1. Conversely, enforced miR-372/373 expression accelerates conversion by directly targeting RELA. These data delineate an NFκB/RELA axis that orchestrates the epigenetic switch to human naïve pluripotency, offering a tractable framework for studying early human development and advancing cell-based therapies.