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Aberrant neurodevelopment in human iPS cell-derived astrocyte-neuron co-culture model of Alexander disease

ABSTRACT: Co-cultures of neurons and astrocytes derived from human iPS cells carrying a GFAP (R239C) mutation - an identified cause of Alexander disease (AxD) - were analyzed with single-cell RNA sequencing to assess cell population composition, differential gene expression, and cell-cell interaction differences in AxD co-cultures compared to controls. Oxygen-glucose deprivation (OGD) challenge was applied to identify differences in stress response. Our results suggested differentiation impairment especially in AxD astrocytes, represented by an enriched population of less differentiated cells and downregulation of mature astrocyte genes in AxD astrocytes-containing co-cultures. Furthermore, AxD co-cultures showed increased stress response represented by upregulation of metallothioneins and increased susceptibility to the OGD challenge.

ORGANISM(S): Homo sapiens

PROVIDER: GSE261110 | GEO | 2024/04/07

REPOSITORIES: GEO

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