A Human IPSC-astroglia Neurodevelopmental Model Reveals Divergent Transcriptomic Patterns in Schizophrenia

Overview

Journal Transl Psychiatry

Specialties Psychiatry
Public Health

Date 2021 Oct 30

PMID 34716291

Citations 12

Authors

Attila Szabo

Ibrahim A Akkouh

Matthieu Vandenberghe

Jordi Requena Osete

Timothy Hughes

Vivi Heine

Olav B Smeland

Joel C Glover

Ole A Andreassen

Srdjan Djurovic

Affiliations

Soon will be listed here.

Abstract

While neurodevelopmental abnormalities have been associated with schizophrenia (SCZ), the role of astroglia in disease pathophysiology remains poorly understood. In the present study, we used a human induced pluripotent stem cell (iPSC)-derived astrocyte model to investigate the temporal patterns of astroglia differentiation during developmental stages critical for SCZ using RNA sequencing. The model generated astrocyte-specific gene expression patterns during differentiation that corresponded well to astroglia-specific expression signatures of in vivo cortical fetal development. Using this model we identified SCZ-specific expression dynamics, and found that SCZ-associated differentially expressed genes were significantly enriched in the medial prefrontal cortex, striatum, and temporal lobe, targeting VWA5A and ADAMTS19. In addition, SCZ astrocytes displayed alterations in calcium signaling, and significantly decreased glutamate uptake and metalloproteinase activity relative to controls. These results implicate novel transcriptional dynamics in astrocyte differentiation in SCZ together with functional changes that are potentially important biological components of SCZ pathology.

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