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.

Thymidine analogs have long been recognized for their ability to randomly incorporate into DNA. However, their significance in the chemical induction of pluripotency (CIP) remains unclear. Here, we investigated the impact of BrdU/IdU incorporation on the transition of cell fate through DNA damage repair (DDR). Our findings reveal a substantial upregulation of reprogramming mediator gene H3K27ac and H3K9ac, as well as global DNA demethylation in response to DDR. This process creates a hypomethylated environment that promotes cell fate transition. We term this mechanism as Epigenetic Reshaping through Damage (ERD). Overall, our study sheds light on the dynamic interplay between thymidine analogs, DDR, and epigenetic modifications, providing valuable insights into the mechanisms underlying cell fate transition.

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. Meanwhile, we found that homologous recombination repair (HRR) pathway causes an overall epigenetic reshaping of cells and enabling them to overcome greater barriers. Moreover, extraembryonic endoderm (XEN) state appears to be a selective response behavior of cells to DNA damage repair (DDR), providing a shortcut for cells to overcome reprogramming barriers, creates a hypomethylated environment that promotes cell fate transition in multiple reprogramming systems. We term this mechanism as Epigenetic Reshaping through Damage (ERD). Conclustion:Overall, our study sheds light on the dynamic interplay between thymidine analogs, DDR, and epigenetic modifications, providing valuable insights into the mechanisms underlying cell fate transition.