Genome-wide expression screening in the cardiac embryonic stem cell test shows additional differentiation routes that are regulated by morpholines and piperidines

• DOI: 10.1016/j.crtox.2022.100086
• Publication Date: 2022-09-13T17:37:24Z
• Authors: R.H. Mennen; N. Hallmark; M. Pallardy; R. Bars; H. Tinwell; A.H. Piersma
• Keywords: Developmental toxicity; Heart development; Morpholine

The cardiac embryonic stem cell test (ESTc) is a well-studied non-animal alternative method based on differentiation inhibition as measure for developmental toxicity of tested chemicals. In the ESTc, heterogenic population generated besides cardiomyocytes. Using full biological domain ESTc may improve sensitivity system, possibly broadening range chemicals which effects can be detected in test. order to our knowledge and chemical applicability domains we applied hypothesis-generating data-driven approach control samples follows. A genome-wide expression screening was performed, using Next Generation Sequencing (NGS), map pathways search predictive embryotoxicity biomarker profile, instead conventional read-out beating included circulatory system development, skeletal heart muscle organ tissue nervous development. Two pesticidal classes, morpholines piperidines, were assessed perturbation NGS. addition anticipated impact cardiomyocyte differentiation, other also regulated, concentration-response fashion. Despite structural differences between morpholine piperidine pairs, their gene effect patterns largely comparable. addition, some chemical-specific regulation observed, help with future mechanistic understanding specific individual compounds. These similar unique regulations profiles by compounds, adds domain, specificity ESTc. Knowledge both contributes optimal placement batteries Integrated Approaches Testing Assessment (IATA).