TY - JOUR
T1 - Intrinsic Immunity Shapes Viral Resistance of Stem Cells
AU - Wu, Xianfang
AU - Dao Thi, Viet Loan
AU - Huang, Yumin
AU - Billerbeck, Eva
AU - Saha, Debjani
AU - Hoffmann, Hans Heinrich
AU - Wang, Yaomei
AU - Silva, Luis A.Vale
AU - Sarbanes, Stephanie
AU - Sun, Tony
AU - Andrus, Linda
AU - Yu, Yingpu
AU - Quirk, Corrine
AU - Li, Melody
AU - MacDonald, Margaret R.
AU - Schneider, William M.
AU - An, Xiuli
AU - Rosenberg, Brad R.
AU - Rice, Charles M.
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/1/25
Y1 - 2018/1/25
N2 - 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. Intrinsic expression of interferon-stimulated genes makes stem cells resistant to infections, preserving their pool throughout the organism's lifespan.
AB - 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. Intrinsic expression of interferon-stimulated genes makes stem cells resistant to infections, preserving their pool throughout the organism's lifespan.
KW - antiviral mechanisms
KW - interferon-stimulated genes
KW - intrinsic immunity
KW - stem cell differentiation
KW - tissue stem cells
KW - tissue tropism
KW - viral infection
UR - http://www.scopus.com/inward/record.url?scp=85039058459&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039058459&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2017.11.018
DO - 10.1016/j.cell.2017.11.018
M3 - Article
C2 - 29249360
AN - SCOPUS:85039058459
SN - 0092-8674
VL - 172
SP - 423-438.e25
JO - Cell
JF - Cell
IS - 3
ER -