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

Acta Neuropathologica Communications

Research

Thomas G. Beach¹  Geidy E. Serrano¹  Yuzhou Chang²  Qi Guo²  Qin Ma³  Yang Li³  Cankun Wang³  Jasmine T. Plummer⁴  Sarah XueYing Song⁴  Chintda Santiskulvong⁴  Douglas W. Scharre⁵  Hongjun Fu⁶  Diana Acosta⁶  Cody Morrison⁶  Liangping Li⁶  Shuo Chen⁷  Dominic Julian⁸  Mark E. Hester⁸  Karen E. Duff⁹  Emir Turkes⁹ 

[1] Banner Sun Health Research Institute, 85351, Sun City, AZ, USA;Biomedical Sciences Graduate Program, Ohio State University, 43210, Columbus, OH, USA;Department of Biomedical Informatics, College of Medicine, Ohio State University, 43210, Columbus, OH, USA;Department of Biomedical Informatics, College of Medicine, Ohio State University, 43210, Columbus, OH, USA;Department of Biomedical Sciences, Cedars-Sinai Medical Center, 90048, Los Angeles, CA, USA;Department of Neurology, Center for Cognitive and Memory Disorders, Center for Neuromodulation, Ohio State University, 43210, Columbus, OH, USA;Department of Neuroscience, College of Medicine, Ohio State University, 43210, Columbus, OH, USA;Department of Neuroscience, College of Medicine, Ohio State University, 43210, Columbus, OH, USA;Biomedical Sciences Graduate Program, Ohio State University, 43210, Columbus, OH, USA;The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children’s Hospital, 43205, Columbus, OH, USA;UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London, UK;

关键词: Spatially resolved transcriptomics;    Alzheimer’s disease;    Vulnerability;    Human middle temporal gyrus;    Microglia;    Oligodendrocytes;    Astrocytes;    Neurons;    Weighted gene co-expression network analyses (WGCNA);    Single-molecule fluorescent in situ hybridization;   

DOI  :  10.1186/s40478-022-01494-6

 received in 2022-10-28, accepted in 2022-12-11,  发布年份 2022

来源: Springer

【 摘 要 】

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 10 × 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.

【 授权许可】

CC BY   
© The Author(s) 2022

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