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Stem cell specific interferon stimulated gene expression is regulated by the formative pluripotency network through IRF1

View ORCID ProfileMerrit Romeike, Stephanie Spach, Marie Huber, Songjie Feng, Gintautas Vainorius, View ORCID ProfileUlrich Elling, View ORCID ProfileChrista Buecker
doi: https://doi.org/10.1101/2021.12.07.471598
Merrit Romeike
1Max Perutz Labs Vienna, Vienna Biocenter (VBC), University of Vienna, Dr.Bohr-Gasse 9, 1030 Vienna, Austria
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  • ORCID record for Merrit Romeike
Stephanie Spach
1Max Perutz Labs Vienna, Vienna Biocenter (VBC), University of Vienna, Dr.Bohr-Gasse 9, 1030 Vienna, Austria
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Marie Huber
1Max Perutz Labs Vienna, Vienna Biocenter (VBC), University of Vienna, Dr.Bohr-Gasse 9, 1030 Vienna, Austria
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Songjie Feng
1Max Perutz Labs Vienna, Vienna Biocenter (VBC), University of Vienna, Dr.Bohr-Gasse 9, 1030 Vienna, Austria
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Gintautas Vainorius
2Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria
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Ulrich Elling
2Institute of Molecular Biotechnology of the Austrian Academy of Science (IMBA), Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria
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Christa Buecker
1Max Perutz Labs Vienna, Vienna Biocenter (VBC), University of Vienna, Dr.Bohr-Gasse 9, 1030 Vienna, Austria
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  • ORCID record for Christa Buecker
  • For correspondence: christa.buecker@univie.ac.at
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Abstract

Stem cells intrinsically express a subset of genes which are normally associated with interferon stimulation, and thus the innate immunity response. Expression of these interferon stimulated genes (ISG) in stem cells is independent of 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 therefore upregulated in the transition from naive to formative pluripotency. IRF1 in turn binds to regulatory regions of a conserved set of ISGs and is required for their faithful expression in formative pluripotent cells. IRF1 also binds to an enhancer of the formative pluripotency transcription factor Oct6 and is partially required for upregulation of Oct6. IRF1 therefore acts as a link between the formative pluripotency network and the regulation of innate immunity genes in formative pluripotency.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 07, 2021.
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Stem cell specific interferon stimulated gene expression is regulated by the formative pluripotency network through IRF1
Merrit Romeike, Stephanie Spach, Marie Huber, Songjie Feng, Gintautas Vainorius, Ulrich Elling, Christa Buecker
bioRxiv 2021.12.07.471598; doi: https://doi.org/10.1101/2021.12.07.471598
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Stem cell specific interferon stimulated gene expression is regulated by the formative pluripotency network through IRF1
Merrit Romeike, Stephanie Spach, Marie Huber, Songjie Feng, Gintautas Vainorius, Ulrich Elling, Christa Buecker
bioRxiv 2021.12.07.471598; doi: https://doi.org/10.1101/2021.12.07.471598

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