Cell
Volume 172, Issue 3, 25 January 2018, Pages 423-438.e25
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Article
Intrinsic Immunity Shapes Viral Resistance of Stem Cells

https://doi.org/10.1016/j.cell.2017.11.018Get rights and content
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Highlights

  • Pluri-/multipotent stem cells exhibit intrinsic expression of ISGs

  • Different stem cells express cell-type-specific groups of ISGs

  • Intrinsically expressed ISGs mediate antiviral resistance ex vivo and in vivo

  • Dynamic expression of ISGs is conserved across species

Summary

Stem cells are highly resistant to viral infection compared to their differentiated progeny; however, the mechanism is mysterious. Here, we analyzed gene expression in mammalian stem cells and cells at various stages of differentiation. We find that, conserved across species, stem cells express a subset of genes previously classified as interferon (IFN) stimulated genes (ISGs) but that expression is intrinsic, as stem cells are refractory to interferon. This intrinsic ISG expression varies in a cell-type-specific manner, and many ISGs decrease upon differentiation, at which time cells become IFN responsive, allowing induction of a broad spectrum of ISGs by IFN signaling. Importantly, we show that intrinsically expressed ISGs protect stem cells against viral infection. We demonstrate the in vivo importance of intrinsic ISG expression for protecting stem cells and their differentiation potential during viral infection. These findings have intriguing implications for understanding stem cell biology and the evolution of pathogen resistance.

Keywords

intrinsic immunity
interferon-stimulated genes
stem cell differentiation
tissue stem cells
antiviral mechanisms
viral infection
tissue tropism

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