The flame retardant triphenyl phosphate induces varying responses in genetically diverse mouse induced pluripotent stem cells

Forward genetic screens of genetically diverse cell populations can be used to identify the precise genetic variants that drive response variation, but such screens are limited by the lack of available genetically diverse human derived cell panels. Cell lines from laboratory mouse genetic reference populations like the Diversity Outbred (DO) population are genetically diverse and powered for genetic mapping but also offer the significant advantage of in vitro / in vivo trait correlation and in vivo validation using genetically matched individuals.

These diverse cell panels are especially beneficial for studying early developmental effects of chemical exposures. We created a panel of induced pluripotent stem cells (iPSCs) derived from the Diversity Outbred mouse population to enable genetic analysis of cellular phenotypes. Cells were exposed to triphenyl phosphate (TPHP), an organophosphate flame retardant that has been linked to numerous adverse developmental effects, to identify cellular responses associated with developmental exposure risk.