Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease
Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease
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DOI：
10.1016/j.cell.2020.06.038
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发表时间：
2020-08-20
期刊：
影响因子：
64.5
通讯作者：
De Strooper, Bart
中科院分区：
文献类型：
--
作者：
Chen, Wei-Ting;Lu, Ashley;De Strooper, Bart
虽然复杂的炎症样改变观察周围的淀粉样斑块的阿尔茨海默氏病（AD），很少有人知道的分子变化和细胞的相互作用，这种反应的特点，我们在这里调查，在AD小鼠模型中，在组织域中发生的转录变化在100 μ m直径周围的淀粉样斑块使用空间转录组学。我们证明了早期改变的基因共表达网络富含髓鞘和少突胶质细胞基因（OLIGs），而斑块诱导的基因（PIGs）的多细胞基因共表达网络涉及补体系统，氧化应激，溶酶体和炎症是突出的疾病的后期阶段。我们使用小鼠和人脑切片上的原位测序证实了在细胞水平上观察到的大多数改变。全基因组空间转录组学分析提供了一种前所未有的方法来解开AD和其他脑部疾病的致病标志附近的失调细胞网络。
Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response, We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-mu m diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.