Influence of Alzheimer's disease related neuropathology on local microenvironment gene expression in the human inferior temporal cortex.

Autor: Kwon SH; The Biochemistry, Cellular, and Molecular Biology Graduate Program, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA., Parthiban S; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA., Tippani M; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Divecha HR; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Eagles NJ; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Lobana JS; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Williams SR; 10x Genomics, Pleasanton, CA, USA., Mak M; 10x Genomics, Pleasanton, CA, USA., Bharadwaj RA; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Kleinman JE; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Hyde TM; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA., Page SC; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA., Hicks SC; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.; Malone Center for Engineering in Healthcare, Johns Hopkins University, Baltimore, MD, USA., Martinowich K; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.; The Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, USA., Maynard KR; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA., Collado-Torres L; Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA.
Jazyk: angličtina
Zdroj: GEN biotechnology [GEN Biotechnol] 2023 Oct; Vol. 2 (5), pp. 399-417. Date of Electronic Publication: 2023 Oct 16.
DOI: 10.1089/genbio.2023.0019
Abstrakt: Neuropathological lesions in the brains of individuals affected with neurodegenerative disorders are hypothesized to trigger molecular and cellular processes that disturb homeostasis of local microenvironments. Here, we applied the 10x Genomics Visium Spatial Proteogenomics (Visium-SPG) platform, which couples spatial gene expression with immunofluorescence protein co-detection, to evaluate its ability to quantify changes in spatial gene expression with respect to amyloid-β (Aβ) and hyperphosphorylated tau (pTau) pathology in post-mortem human brain tissue from individuals with Alzheimer's disease (AD). We identified transcriptomic signatures associated with proximity to Aβ in the human inferior temporal cortex (ITC) during late-stage AD, which we further investigated at cellular resolution with combined immunofluorescence and single molecule fluorescent in situ hybridization (smFISH). The study provides a data analysis workflow for Visium-SPG, and the data represent a proof-of-principal for the power of multi-omic profiling in identifying changes in molecular dynamics that are spatially-associated with pathology in the human brain. We provide the scientific community with web-based, interactive resources to access the datasets of the spatially resolved AD-related transcriptomes at https://research.libd.org/Visium_SPG_AD/.
Competing Interests: Author disclosure statement SRW and MM are employees of 10x Genomics. All other authors declare no conflicts of interest.
Databáze: MEDLINE
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