Development of Antiviral Innate Immunity During In Vitro Differentiation of Mouse Embryonic Stem Cells

William D'Angelo, University of Southern Mississippi
Dhiraj Acharya, University of Southern Mississippi
Ruoxing Wang, University of Pennsylvania School of Medicine
Jundi Wang, University of Southern Mississippi
Chandan Gurung, University of Southern Mississippi
Bohan Chen, University of Southern Mississippi
Fengwei Bai, University of Southern Mississippi
Yan-Lin Guo, University of Southern Mississippi

Abstract

The innate immunity of embryonic stem cells (ESCs) has recently emerged as an important issue in ESC biology and in ESC-based regenerative medicine. We have recently reported that mouse ESCs (mESCs) do not have a functional type I interferon (IFN)-based antiviral innate immunity. They are deficient in expressing IFN in response to viral infection and have limited ability to respond to IFN. Using fibroblasts (FBs) as a cell model, the current study investigated the development of antiviral mechanisms during in vitro differentiation of mESCs. We demonstrate that mESC-differentiated FBs (mESC-FBs) share extensive similarities with naturally differentiated FBs in morphology, marker expression, and growth pattern, but their development of antiviral mechanisms lags behind. Nonetheless, the antiviral mechanisms are inducible during mESC differentiation as demonstrated by the transition of nuclear factor kappa B (NFκB), a key transcription factor for IFN expression, from its inactive state in mESCs to its active state in mESC-FBs and by increased responses of mESC-FBs to viral stimuli and IFN during their continued in vitro propagation. Together with our previously published study, the current data provide important insights into molecular basis for the deficiency of IFN expression in mESCs and the development of antiviral innate immunity during mESC differentiation.