학술논문
Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer's disease.
Document Type
Academic Journal
Author
Chen S; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, 43210, USA.; Biomedical Sciences Graduate Program, Ohio State University, Columbus, OH, 43210, USA.; Chang Y; Biomedical Sciences Graduate Program, Ohio State University, Columbus, OH, 43210, USA.; Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, 43210, USA.; Li L; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, 43210, USA.; Acosta D; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, 43210, USA.; Li Y; Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, 43210, USA.; Guo Q; Biomedical Sciences Graduate Program, Ohio State University, Columbus, OH, 43210, USA.; Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, 43210, USA.; Wang C; Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, 43210, USA.; Turkes E; UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London, UK.; Morrison C; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, 43210, USA.; Julian D; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, 43205, USA.; Hester ME; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, 43205, USA.; Scharre DW; Department of Neurology, Center for Cognitive and Memory Disorders, Center for Neuromodulation, Ohio State University, Columbus, OH, 43210, USA.; Santiskulvong C; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.; Song SX; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.; Plummer JT; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.; Serrano GE; Banner Sun Health Research Institute, Sun City, AZ, 85351, USA.; Beach TG; Banner Sun Health Research Institute, Sun City, AZ, 85351, USA.; Duff KE; UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London, UK.; Ma Q; Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, 43210, USA. Qin.Ma@osumc.edu.; Fu H; Department of Neuroscience, College of Medicine, Ohio State University, Columbus, OH, 43210, USA. Hongjun.Fu@osumc.edu.
Source
Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(© 2022. The Author(s).)
(© 2022. The Author(s).)