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Transient upregulation of IRF1 during exit from naive pluripotency confers viral protection
Author(s) -
Romeike Merrit,
Spach Stephanie,
Huber Marie,
Feng Songjie,
Vainorius Gintautas,
Elling Ulrich,
Versteeg Gjis A,
Buecker Christa
Publication year - 2022
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202255375
Subject(s) - irf1 , biology , interferon , microbiology and biotechnology , induced pluripotent stem cell , innate immune system , stem cell , interferon regulatory factors , downregulation and upregulation , regulation of gene expression , embryonic stem cell , gene , immunology , genetics , gene expression , immune system
Abstract Stem cells intrinsically express a subset of genes which are normally associated with interferon stimulation and the innate immune response. However, the expression of these interferon‐stimulated genes (ISG) in stem cells is independent from external stimuli such as viral infection. Here, we show that the interferon regulatory factor 1, Irf1 , is directly controlled by the murine formative pluripotency gene regulatory network and transiently upregulated during the transition from naive to formative pluripotency. IRF1 binds to regulatory regions of a conserved set of ISGs and is required for their faithful expression upon exit from naive pluripotency. We show that in the absence of IRF1, cells exiting the naive pluripotent stem cell state are more susceptible to viral infection. Irf1 therefore acts as a link between the formative pluripotency network, regulation of innate immunity genes, and defense against viral infections during formative pluripotency.