Journal
CELL
Volume 172, Issue 3, Pages 423-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2017.11.018
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Funding
- NIH [R01-AI091707, U19 AI111825, DK100810]
- John C. Whitehead Presidential Fellowship
- NSF of China [81530005]
- Greenberg Medical Research Institute
- Starr Foundation
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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.
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