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Region specific astrocyte response to mutant GFAP in Alexander disease model mice during postnatal development.

ABSTRACT: Region specific astrocyte response to mutant GFAP in Alexander disease model mice during postnatal development.

PROVIDER: PRJNA816975 | ENA |

REPOSITORIES: ENA

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Region specific astrocyte response to mutant GFAP in Alexander disease model mice during postnatal development.

Project description:Gene expression analysis was performed in Gfap+/+, Gfap+/R236H, and mGFAPTg170-2 transgenic mice, using the Aldh1l1-eGFP-L10a transgenic line (JD130) to isolate translating ribosomes and purify astrocyte specific transcripts for RNAseq.

2023-01-17 | GSE198817 | GEO

Microglia sense astrocyte dysfunction and prevent disease progression in an Alexander disease model

Project description:Alexander disease is a neurodegenerative diseases caused by mutations of GFAP, an astrocyte-specific gene. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of astrocytes.

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Project description:Gene expression analysis was performed in mouse models with Alexander disease associated GFAP mutations

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Identification of genes associated with the astrocyte-specific gene Gfap during astrocyte differentiation

Project description:Chromosomes and genes are non-randomly arranged within the mammalian cell nucleus. Clustering of genes is of great significance in transcriptional regulation. However, the relevance of gene clustering in their expression during differentiation of neural precursor cells (NPCs) into astrocytes remains unclear. We performed a genome-wide enhanced circular chromosomal conformation capture (e4C) to screen genes associated with an astrocyte-specific gene, glial fibrillary acidic protein (Gfap), during astrocyte differentiation. We identified 13 genes that were specifically associated with Gfap and expressed in NPC-derived astrocytes. These results provide evidence for functional significance of gene clustering in transcriptional regulation during NPCs differentiation. comparison of NPCs vs LIF+ vs LIF- cells.

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

Project description: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.

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Identification of genes associated with the astrocyte-specific gene Gfap during astrocyte differentiation

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Aberrant neurodevelopment in human iPS cell-derived neural organoid model of Alexander disease

Project description:3D-cultured unguided neural and cortical organoids derived from human iPS cells carrying a GFAP (R239C) mutation - an identified cause of Alexander disease (AxD) - and their isogenic controls were analyzed with scRNA-seq to investigate the effect of the GFAP mutation on brain development, cell type composition, and gene expression. Results of this analysis showed impaired astro- and neurogenesis in both types of organoids (unguided and cortical), including a lack of cells acquiring the astrocyte fate, and an increased abundance of cells differentiating into lineages other than neuroectodermal. The results also suggested dysregulation of extracellular matrix, membrane, and cytoskeleton components, which might have also affected their differentiation trajectories.

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Project description:Genetic modifiers of GFAP expression in mouse models of Alexander disease

| PRJNA808603 | ENA