Gene interactions analysis of brain spatial transcriptome for Alzheimer's disease

作者：Shengran Wang, Jonathan Greenbaum, Chuan Qiu, Russell H. Swerdlow, Mohammad Haeri, Yun Gong, Hui Shen, Hong‐Mei Xiao, Hong‐Wen Deng · 发表于：Genes & Diseases · 年份：2024 · DOI：10.1016/j.gendis.2024.101337 · 被引用次数：12 · 研究领域：Single-cell and spatial transcriptomics、Bioinformatics and Genomic Networks、Gene expression and cancer classification

Recent studies have explored the spatial transcriptomics patterns of Alzheimer's disease (AD) brain by spatial sequencing in mouse models, enabling the identification of unique genome-wide transcriptomic features associated with different spatial regions and pathological status. However, the dynamics of gene interactions that occur during amyloid-β accumulation remain largely unknown. In this study, we performed analyses on ligand-receptor communication, transcription factor regulatory network, and spot-specific network to reveal the dependence and the dynamics of gene associations/interactions on spatial regions and pathological status with mouse and human brains. We first used a spatial transcriptomics dataset of the AppNL-G-F knock-in AD and wild-type mouse model. We revealed 17 ligand-receptor pairs with opposite tendencies throughout the amyloid-β accumulation process and showed the specific ligand-receptor interactions across the hippocampus layers at different extents of pathological changes. We then identified nerve function related transcription factors in the hippocampus and entorhinal cortex, as well as genes with different transcriptomic association degrees in AD versus wild-type mice. Finally, another independent spatial transcriptomics dataset from different AD mouse models and human single-nuclei RNA-seq data/AlzData database were used for validation. This is the first study to identify various gene associations throughout amyloid-β accumulation based on spatia...