iGEM as a human iPS cell-based global epigenetic modulation detection assay provides throughput characterization of chemicals affecting DNA methylation

Abstract

Chemical-induced dysregulation of DNA methylation during the fetal period is known to contribute to developmental disorders or increase the risk of certain diseases later in life. In this study, we developed an iGEM (iPS cell-based global epigenetic modulation) detection assay using human induced pluripotent stem (hiPS) cells that express a fluorescently labeled methyl-CpG-binding domain (MBD), which enables a high-throughput screening of epigenetic teratogens/mutagens. 135 chemicals with known cardiotoxicity and carcinogenicity were categorized according to the MBD signal intensity, which reflects the degree of nuclear spatial distribution/concentration of DNA methylation. Further biological characterization through machine-learning analysis that integrated genome-wide DNA methylation, gene expression profiling, and knowledge-based pathway analysis revealed that chemicals with hyperactive MBD signals strongly associated their effects on DNA methylation and expression of genes involved in cell cycle and development. These results demonstrated that our MBD-based integrated analytical system is a powerful framework for detecting epigenetic compounds and providing mechanism insights of pharmaceutical development for sustainable human health.

A molecular imprinting electrochemical sensor for detection of anticancer drug amsacrine

“…Moreover, these techniques are not suitable for real-time monitoring or point-of-care applications (Yamamoto et al, 2019). Hence, there is a pressing need for the development of cost-effective, user-friendly and rapid analytical tools for amsacrine detection (Onecha et al, 2020;Otsuka et al, 2023;Spînu et al, 2021).…”

“…Hence, there is a pressing need for the development of cost-effective, user-friendly and rapid analytical tools for amsacrine detection (Onecha et al. , 2020; Otsuka et al. , 2023; Spînu et al.…”