For many years, scientists have observed paradoxical behavior of stem cells. In their differentiated offspring, signaling molecules called interferons are activated upon viral infection and initiate a signaling cascade that results in the expression of antiviral genes, or interferon stimulated genes (ISGs). Stem cells, on the other hand, do not respond to interferon stimulation but are still remarkably resistant to viral infection. Accumulating evidence has indicated that the innate immune system, including ISGs, is constitutively turned on in stem cells. Precisely how the expression of ISGs is controlled in the absence of interferon signaling, however, has remained enigmatic.
Merrit Romeike, a PhD student in the Bücker lab, first set out to identify factors that are involved in the exit from naïve pluripotency, a key developmental step of stem cells. To this end she performed a CRISPR knockout screen to identify factors that influence the exit from pluripotency. One of the top hits from the screen was a gene called Irf1, an ISG which encodes a transcription factor. Utilizing a simplified in vitro differentiation system with mouse embryonic stem cells, the scientist discovered that while it does not directly control the cell state transition, it is nevertheless connected to the genetic network at the heart of the pluripotent cell state. “We could show that Irf1 is directly controlled by two pluripotency genes called Oct4 and Otx2 through a stem cell-specific enhancer”, explains Merrit Romeike.
Oct4 and Otx2 are both important transcription factors that safeguard the pluripotent cell state. Irf1 in turn controls a subset of ISGs in stem cells that confer antiviral protection. “The same genes that help cells to keep their identity also upregulate the genes which are required for the viral defense”, says Merrit Romeike. In vivo data further show that this intrinsic upregulation is transient and confined to a short timeframe. “Before implantation of the embryo into the uterus it is surrounded by the zona pellucida, an extra layer that protects the embryo for example from viral infection. But during implantation, the embryo hatches from that layer and attaches to the uterine wall. We found that exactly during this period of hatching and implanting, the intrinsic network upregulates Irf1“, says Merrit Romeike. “We suggest that, in vivo, the prophylactic priming of the antiviral defense system might protect the embryo at this vulnerable moment in development”. However, further research is necessary to confirm this observation in living organisms.
Publication:
Merrit Romeike, Stephanie Spach, Marie Huber, Songjie Feng, Gintautas Vainorius, Ulrich Elling, Gjis A Versteeg, Christa Buecker: Transient upregulation of IRF1 during exit from naive pluripotency confers viral protection. EMBO Reports 2022
18th Microsymposium on RNA Biology
The „Microsymposium on RNA Biology“ is an international conference that brings together young scientists, junior and senior group leaders, and company representatives from all over the world to present and discuss their latest findings in the exciting field of small RNAs and beyond. The Microsymposium was founded in 2005 and has established itself as the major small RNA meeting in Europe. It is organized by the four research institutions IMBA, IMP, GMI and the Max Perutz Labs as well as by the RNA community of the Vienna BioCenter.
Transformation Reactions of Organic Contaminants and Oxygen: From Field Sites to Reaction Mechanisms
Nickel impact on human health, from bacterial infections to cancer
Multiscale plant bioimaging using advanced microscopy
Parthenogenesis, cryptobiosis, and the survival in extreme environmental conditions
Evading ageing: Mitochondrial and proteostatic adaptations in oocytes
Genomes in Rhodnius prolixus symbiotic system
Stem cells, immune evasion and metastasis in colorectal cancer
Ubiquitin & Friends Symposium 2024
The Ubiquitin & Friends Symposium is an annual international meeting taking place in the beautiful capital of Austria, aiming to bring together scholars from various fields studying ubiquitin/Ubl biology and protein degradation in a personal, family-like atmosphere, as suggested by the name.
The evolution and development of mollusc shells
Unraveling the Complexity of Crossover Regulation in C. elegans
Dynamics of 3D Genome Structure and Function
How superworms can help to solve our plastic waste crisis
Title to be announced
New players in an old pathway: biology of methanogens of the TACK superphylum
Shaping morphogen gradients: from molecules to tissues and back
Title to be announced
Studying stressed cells by in situ structural biology
Exploring Microbial Resilience: Unravelling Escherichia coliand#x27;s Stress Response at the Level of Protein Synthesis
Arbuscular mycorrhiza development and function
Deep homology and deep diversity: Evolving genetic toolkits for making and sensing light
The evolution of cell type identity and tissue microecology at the fetal-maternal interface
The unanticipated roles of PICIs and phages in bacterial evolution
Chemical targeting of subcellular protein localization
Origin and diversification of gut-derived organs in chordates
Job's Dilemma for the Genome: Why Bad Things Happen to Good Chromosomes
Connections between carbon and nitrogen cycling in the ocean
Understanding how the DNA-loop-extruding protein complex Condensin folds a chromatinized genome into mitotic chromosomes
From Roads to Rivers? Occurrence and environmental fate of tire and road wear particles and of tire-related chemicals
FENS 2024 Satellite event: Home cage behavior monitoring at the interface of animal welfare and neuroscience
Striking physiology and cell biology of (marine) environmental microorganisms
Mechanisms controlling maintenance of cohesin dependent loops
Title to be announced