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Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease

ABSTRACT: Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease

PROVIDER: PRJNA909771 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22561782.fastq.gz	Fastqsanger.gz
	SRR22561783.fastq.gz	Fastqsanger.gz
	SRR22561784.fastq.gz	Fastqsanger.gz
	SRR22561785.fastq.gz	Fastqsanger.gz
	SRR22561786.fastq.gz	Fastqsanger.gz

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Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease

Project description:Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer’s disease (AD), but little is known about the molecular mechanisms underlying this regional vulnerability. Here we utilize the 10x Visium platform to define the spatial transcriptomic profile in both AD and control (CT) MTG. We identify unique marker genes for cortical layers and the white matter, and layer-specific differentially expressed genes (DEGs) in human AD compared to CT. Deconvolution of the Visium spots showcases the significant difference in particular cell types among cortical layers and the white matter. Gene co-expression analyses reveal eight gene modules, four of which have significantly altered co-expression patterns in the presence of AD pathology. The co-expression patterns of hub genes and enriched pathways in the presence of AD pathology indicate an important role of cell-cell-communications among microglia, oligodendrocytes, astrocytes, and neurons, which may contribute to the cellular and regional vulnerability in early AD. Using single-molecule fluorescent in situ hybridization, we validated the cell-type-specific expression of three novel DEGs (e.g., KIF5A, PAQR6, and SLC1A3) and eleven previously reported DEGs associated with AD pathology (i.e., amyloid beta plaques and intraneuronal neurofibrillary tangles or neuropil threads) at the single cell level. Our results may contribute to the understanding of the complex architecture and neuronal and glial response to AD pathology of this vulnerable brain region.

2022-12-21 | GSE220442 | GEO

Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer's disease.

Project description: Not available

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DNase-seq from middle frontal gyrus (ENCSR318PRQ)

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Project description:The human hippocampus, a center of learning and memory, has a complex architecture with high cellular and molecular heterogeneity. We present the first spatially resolved atlas of human hippocampus at the genome scale. Spatial transcriptome sequencing on 10 hippocampi identified the hippocampal sub-fields and cell types in the dentate gyrus and the cornu Ammonis regions. We deconvoluted the cellular composition in each pixel to build a gene expression landscape of each cell subtype. Psychiatrically healthy brains were compared with brains from subjects with major depressive disorder (MDD) to identify differentially modulated pathogenic genes and pathways in a region-specific manner. We observed surprisingly high variability of RNA splicing in MDD compared with control. RNA velocity analysis suggested a model for how transcriptomic instability in MDD contributes to a high inter-patient heterogeneity particularly in the pyramidal neurons. Spatially resolved chromatin accessibility profiling further identified potential epigenetic underpinnings implicated in MDD molecular neuropathology.

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Spatially resolved multi-omic profiling of human hippocampus reveals region-specific alterations in major depressive disorder [ATAC-seq]

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Alzheimer's disease DNA (hydroxy) methylome in the brain: OXT methylation as a preclinical marker.

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