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Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer's disease.
Acta Neuropathol Commun. 2022 12 21; 10(1):188.AN

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.

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Authors+Show Affiliations

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.

MeSH

HumansAlzheimer DiseaseAmyloid beta-PeptidesIn Situ Hybridization, FluorescenceKinesinsTemporal LobeTranscriptome

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

36544231

Citation

Chen, Shuo, et al. "Spatially Resolved Transcriptomics Reveals Genes Associated With the Vulnerability of Middle Temporal Gyrus in Alzheimer's Disease." Acta Neuropathologica Communications, vol. 10, no. 1, 2022, p. 188.
Chen S, Chang Y, Li L, et al. Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer's disease. Acta Neuropathol Commun. 2022;10(1):188.
Chen, S., Chang, Y., Li, L., Acosta, D., Li, Y., Guo, Q., Wang, C., Turkes, E., Morrison, C., Julian, D., Hester, M. E., Scharre, D. W., Santiskulvong, C., Song, S. X., Plummer, J. T., Serrano, G. E., Beach, T. G., Duff, K. E., Ma, Q., & Fu, H. (2022). Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer's disease. Acta Neuropathologica Communications, 10(1), 188. https://doi.org/10.1186/s40478-022-01494-6
Chen S, et al. Spatially Resolved Transcriptomics Reveals Genes Associated With the Vulnerability of Middle Temporal Gyrus in Alzheimer's Disease. Acta Neuropathol Commun. 2022 12 21;10(1):188. PubMed PMID: 36544231.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer's disease. AU - Chen,Shuo, AU - Chang,Yuzhou, AU - Li,Liangping, AU - Acosta,Diana, AU - Li,Yang, AU - Guo,Qi, AU - Wang,Cankun, AU - Turkes,Emir, AU - Morrison,Cody, AU - Julian,Dominic, AU - Hester,Mark E, AU - Scharre,Douglas W, AU - Santiskulvong,Chintda, AU - Song,Sarah XueYing, AU - Plummer,Jasmine T, AU - Serrano,Geidy E, AU - Beach,Thomas G, AU - Duff,Karen E, AU - Ma,Qin, AU - Fu,Hongjun, Y1 - 2022/12/21/ PY - 2022/10/28/received PY - 2022/12/11/accepted PY - 2022/12/21/entrez PY - 2022/12/22/pubmed PY - 2022/12/24/medline KW - Alzheimer’s disease KW - Astrocytes KW - Human middle temporal gyrus KW - Microglia KW - Neurons KW - Oligodendrocytes KW - Single-molecule fluorescent in situ hybridization KW - Spatially resolved transcriptomics KW - Vulnerability KW - Weighted gene co-expression network analyses (WGCNA) SP - 188 EP - 188 JF - Acta neuropathologica communications JO - Acta Neuropathol Commun VL - 10 IS - 1 N2 - 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. SN - 2051-5960 UR - https://www.unboundmedicine.com/medline/citation/36544231/Spatially_resolved_transcriptomics_reveals_genes_associated_with_the_vulnerability_of_middle_temporal_gyrus_in_Alzheimer's_disease_ DB - PRIME DP - Unbound Medicine ER -