Intrinsic Immunity Shapes Viral Resistance of Stem Cells

Numerous studies have demonstrated that stem cells are more resistant to virus infection than their differentiated progenies; however, the nature of this differential virus resistance remains a mystery. Here we analyzed gene expression in both mammalian stem cells and cells at various stages of differentiation. We found that stem cells intrinsically express a subset of interferon stimulated genes (ISGs) and that this property is conserved across species. We show that ISG expression is truly intrinsic, as stem cells are refractory to interferon (IFN). Further, ISG expression varies in a cell type-specific manner and decreases as cells differentiate. We show that once cell differentiate they become IFN-responsive and a broad spectrum of ISGs are then induced by canonical IFN signaling. Importantly, we also show that intrinsically expressed ISGs protect stem cells from virus infection. Finally, we performed in vivo experiments to show that protecting stem cells from virus infection is critical because stem cells are needed to regenerate tissues damaged by virus infection. Our findings have important implications for understanding both stem cell biology and the evolution of innate immunity. Overall design: mRNA profiles for hESC-derived cells and primary cells were generated by deep sequencing, in duplicate or triplicate, using IlluminaHiSeq 2000.