دورية أكاديمية

Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer's Disease Patients

التفاصيل البيبلوغرافية
العنوان: Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer's Disease Patients
المؤلفون: Lampinen, Riikka, Fazaludeen, Mohammad Feroze, Avesani, Simone, Ord, Tiit, Penttila, Elina, Lehtola, Juha-Matti, Saari, Toni, Hannonen, Sanna, Saveleva, Liudmila, Kaartinen, Emma, Fernandez Acosta, Francisco, Cruz-Haces, Marcela, Lopponen, Heikki, Mackay-Sim, Alan, Kaikkonen, Minna U., Koivisto, Anne M., Malm, Tarja, White, Anthony R., Giugno, Rosalba, Chew, Sweelin, Kanninen, Katja M.
المساهمون: Department of Neurosciences, Neurologian yksikkö, HUS Neurocenter, Geriatrian yksikkö
بيانات النشر: MDPI
سنة النشر: 2022
المجموعة: Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto
مصطلحات موضوعية: Alzheimer's disease, olfactory mucosa, amyloid beta, single-cell RNA-sequencing, mitochondria, BETA, EXPRESSION, BRAIN, TAU, NEUROGENESIS, DYSFUNCTION, CONSORTIUM, EPITHELIUM, ESTABLISH, REGISTRY, 3112 Neurosciences, 3124 Neurology and psychiatry, 1182 Biochemistry, cell and molecular biology
الوصف: Olfaction is orchestrated by olfactory mucosal cells located in the upper nasal cavity. Olfactory dysfunction manifests early in several neurodegenerative disorders including Alzheimer's disease, however, disease-related alterations to the olfactory mucosal cells remain poorly described. The aim of this study was to evaluate the olfactory mucosa differences between cognitively healthy individuals and Alzheimer's disease patients. We report increased amyloid-beta secretion in Alzheimer's disease olfactory mucosal cells and detail cell-type-specific gene expression patterns, unveiling 240 differentially expressed disease-associated genes compared to the cognitively healthy controls, and five distinct cell populations. Overall, alterations of RNA and protein metabolism, inflammatory processes, and signal transduction were observed in multiple cell populations, suggesting their role in Alzheimer's disease-related olfactory mucosa pathophysiology. Furthermore, the single-cell RNA-sequencing proposed alterations in gene expression of mitochondrially located genes in AD OM cells, which were verified by functional assays, demonstrating altered mitochondrial respiration and a reduction of ATP production. Our results reveal disease-related changes of olfactory mucosal cells in Alzheimer's disease and demonstrate the utility of single-cell RNA sequencing data for investigating molecular and cellular mechanisms associated with the disease. ; Peer reviewed
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
العلاقة: This research was funded by The Academy of Finland (295425), The Sigrid Juselius Foundation, The Finnish Cultural Foundation, The Inkeri and Mauri Vanska Foundation, The Yrjo Jahnsson Foundation, The Saastamoinen Foundation and The Finnish Brain Foundation. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 814978.; Lampinen , R , Fazaludeen , M F , Avesani , S , Ord , T , Penttila , E , Lehtola , J-M , Saari , T , Hannonen , S , Saveleva , L , Kaartinen , E , Fernandez Acosta , F , Cruz-Haces , M , Lopponen , H , Mackay-Sim , A , Kaikkonen , M U , Koivisto , A M , Malm , T , White , A R , Giugno , R , Chew , S & Kanninen , K M 2022 , ' Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer's Disease Patients ' , Cells , vol. 11 , no. 4 , 676 . https://doi.org/10.3390/cells11040676Test; 9418c0ce-00e1-44de-8e9b-67d358dc255d; http://hdl.handle.net/10138/342420Test; 000763939800001
الإتاحة: http://hdl.handle.net/10138/342420Test
حقوق: cc_by ; openAccess ; info:eu-repo/semantics/openAccess
رقم الانضمام: edsbas.86CA7B16
قاعدة البيانات: BASE