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Intrinsic Immunity Shapes Viral Resistance of Stem Cells

Wu, Xianfang ; Dao Thi, Viet Loan ; Huang, Yumin ; Billerbeck, Eva ; Saha, Debjani ; Hoffmann, Hans-Heinrich ; Wang, Yaomei ; Silva, Luis A. Vale ; Sarbanes, Stephanie ; Sun, Tony ; Andrus, Linda ; Yu, Yingpu ; Quirk, Corrine ; Li, Melody ; MacDonald, Margaret R. ; Schneider, William M. ; An, Xiuli ; Rosenberg, Brad R. ; Rice, Charles M.

Cell, 2018-01, Vol.172 (3), p.423-438.e25 [Peer Reviewed Journal]

United States: Elsevier Inc

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Title:
Intrinsic Immunity Shapes Viral Resistance of Stem Cells
Author: Wu, Xianfang ; Dao Thi, Viet Loan ; Huang, Yumin ; Billerbeck, Eva ; Saha, Debjani ; Hoffmann, Hans-Heinrich ; Wang, Yaomei ; Silva, Luis A. Vale ; Sarbanes, Stephanie ; Sun, Tony ; Andrus, Linda ; Yu, Yingpu ; Quirk, Corrine ; Li, Melody ; MacDonald, Margaret R. ; Schneider, William M. ; An, Xiuli ; Rosenberg, Brad R. ; Rice, Charles M.
Subjects: Animals ; antiviral mechanisms ; Cells, Cultured ; Female ; HEK293 Cells ; Humans ; Immunity, Innate ; interferon-stimulated genes ; Interferons - metabolism ; intrinsic immunity ; Male ; Mice ; Mice, Inbred NOD ; Pluripotent Stem Cells - immunology ; Pluripotent Stem Cells - virology ; Species Specificity ; stem cell differentiation ; tissue stem cells ; tissue tropism ; viral infection ; Virus Diseases - immunology
Is Part Of: Cell, 2018-01, Vol.172 (3), p.423-438.e25
Notes: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Description: 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. [Display omitted] •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 Intrinsic expression of interferon-stimulated genes makes stem cells resistant to infections, preserving their pool throughout the organism’s lifespan.
Publisher: United States: Elsevier Inc
Language: English

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Intrinsic Immunity Shapes Viral Resistance of Stem Cells

United States: Elsevier Inc

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