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bioRxiv · 10.1101/2020.05.23.112748

Modeling Human Peripheral Myelin Fully from Pluripotent Stem Cells and Immune-mediated Neuropathy In Vitro using ZIKA Virus

Mirakhori, F.·Xu, Z.·Qin, C.-F.
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Abstract

The generation of in vitro model of human peripheral myelin development and associated disease from human pluripotent stem cells (hPSCs) has been a challenge so far. In addition, the underlying mechanism for ZIKA virus (ZIKV) infection incurred Guillain-Barre syndrome (GBS) remains unexplored due to the lack of a suitable model. Here, we report the de novo generation of a human peripheral myelination model with competent Schwann cells (SCs). Those human SCs generated from hPSCs via compound screening were capable of forming compact myelin both in vitro and in vivo. We found ZIKV infection caused GBS-like events in vitro including myelin sheath degeneration, as well as dysregulated transcriptional profile including the activated cell death pathways and cytokine production. These effects could be partially reversed by several pharmacological inhibitors. Our model therefore provides a new and robust tool for studying the pathogenic mechanisms and developing of therapeutic strategies for related neuropathies.

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Mirakhori, F., Xu, Z., Qin, C.-F.. 2020-05-23. Modeling Human Peripheral Myelin Fully from Pluripotent Stem Cells and Immune-mediated Neuropathy In Vitro using ZIKA Virus. https://doi.org/10.1101/2020.05.23.112748

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