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Type I interferon response impairs differentiation potential of pluripotent stem cells
Julie Eggenberger1, Daniel Blanco-Melo1, Maryline Panis1
1Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
Summary
Pluripotent stem cells avoid antiviral defenses, but restoring them in iPSCs disrupts development. This suggests the interferon system and pluripotency are incompatible, explaining stem cells' unique antiviral response.
Area of Science:
- Immunology
- Stem Cell Biology
- Virology
Background:
- Pluripotent stem cells, including induced pluripotent stem cells (iPSCs), do not mount a canonical type I interferon (IFN-I) response upon viral infection.
- This lack of response is crucial for understanding stem cell biology and potential therapeutic applications.
Purpose of the Study:
- To investigate the consequences of restoring antiviral defenses in iPSCs.
- To determine the compatibility of the IFN-I system with pluripotency.
Main Methods:
- Characterization of iPSCs and their differentiated counterparts.
- Engineering iPSCs to express a virus-activated transcription factor for inducible antiviral response.
- Analysis of gene expression and trilineage differentiation post-antiviral induction.
Main Results:
- iPSCs, unlike fibroblasts, failed to respond to viral stimuli or IFN-I.
- Restoring antiviral defenses in iPSCs led to upregulation of IFN-I-stimulated genes.
- Antiviral induction in iPSCs caused gene dysregulation across all three germ layers and impaired differentiation, despite maintaining pluripotency markers.
Conclusions:
- The IFN-I system and pluripotency appear incompatible.
- Temporal induction of antiviral responses in iPSCs primes them away from pluripotency and leads to aberrant gene expression during differentiation.
- This incompatibility explains why stem cells do not utilize canonical antiviral systems.
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