Interferon-γ signaling in human iPSC–derived neurons recapitulates neurodevelopmental disorder phenotypes
Warre-Cornish K, Perfect L, Nagy R, Duarte RRR, Reid MJ, Raval P, Mueller A, Evans AL, Couch A, Ghevaert C, Mcalonan G, Loth E, Murphy D, Powell TR, Vernon AC, Srivastava DP, Price J (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 6
Article Number: eaay9506
Journal Issue: 34
Abstract
Maternal immune activation increases the risk of neurodevelopmental disorders. Elevated cytokines, such as interferon-γ (IFN-γ), in offspring’s brains play a central role. IFN-γ activates an antiviral cellular state, limiting viral entry and replication. Moreover, IFN-γ is implicated in brain development. We tested the hypothesis that IFN-γ signaling contributes to molecular and cellular phenotypes associated with neurodevelopmental disorders. Transient IFN-γ treatment of neural progenitors derived from human induced pluripotent stem cells increased neurite outgrowth. RNA sequencing analysis revealed that major histocompatibility complex class I (MHCI) genes were persistently up-regulated through neuronal differentiation—an effect that was mediated by IFN-γ-induced promyelocytic leukemia protein (PML) nuclear bodies. Critically, IFN-γ-induced neurite outgrowth required both PML and MHCI. We also found evidence that IFN-γ disproportionately altered the expression of genes associated with schizophrenia and autism, suggesting convergence between genetic and environmental risk factors. Together, these data implicate IFN-γ signaling in neurodevelopmental disorder etiology.
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United Kingdom (GB)How to cite
APA:
Warre-Cornish, K., Perfect, L., Nagy, R., Duarte, R.R.R., Reid, M.J., Raval, P.,... Price, J. (2020). Interferon-γ signaling in human iPSC–derived neurons recapitulates neurodevelopmental disorder phenotypes. Science Advances, 6(34). https://doi.org/10.1126/sciadv.aay9506
MLA:
Warre-Cornish, Katherine, et al. "Interferon-γ signaling in human iPSC–derived neurons recapitulates neurodevelopmental disorder phenotypes." Science Advances 6.34 (2020).
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