Tetrahedral DNA Nanomaterial Regulates the Biological Behaviors of Adipose-Derived Stem Cells via DNA Methylation on Dlg3

As a simple and classical three-dimensional shape, tetrahedral DNA nanostructures (TDNs) can provide robust properties for better stability and can serve as a versatile platform for biosensing and drug delivery. More in-depth, its safety should be assessed by sensitive detection methods. However, the effect of TDNs at the epigenetic level has not received much attention. Here, DNA methylation alteration in adipose-derived stem cells (ASCs) after exposure to TDNs was comprehensively evaluated. The results from reduced representation bisulfite sequencing, bisulfite-specific polymerase chain reaction, and further gene function analysis revealed that TDNs induced a few differentially methylated regions where negatively correlated gene expressions occur. Moreover, TDNs facilitated ASC proliferation and attenuated apoptosis via DNA hypermethylation of the Dlg3 gene promotor. This study may help pave the way for potential applications with the nanosafety of TDNs and offer deep insights into the proliferation promotion effect and antiapoptosis ability of TDNs.