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

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...

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Autores principales: Lampinen, Riikka, Fazaludeen, Mohammad Feroze, Avesani, Simone, Örd, Tiit, Penttilä, Elina, Lehtola, Juha-Matti, Saari, Toni, Hannonen, Sanna, Saveleva, Liudmila, Kaartinen, Emma, Fernández Acosta, Francisco, Cruz-Haces, Marcela, Löppönen, Heikki, Mackay-Sim, Alan, Kaikkonen, Minna U., Koivisto, Anne M., Malm, Tarja, White, Anthony R., Giugno, Rosalba, Chew, Sweelin, Kanninen, Katja M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870160/
https://www.ncbi.nlm.nih.gov/pubmed/35203328
http://dx.doi.org/10.3390/cells11040676
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author Lampinen, Riikka
Fazaludeen, Mohammad Feroze
Avesani, Simone
Örd, Tiit
Penttilä, Elina
Lehtola, Juha-Matti
Saari, Toni
Hannonen, Sanna
Saveleva, Liudmila
Kaartinen, Emma
Fernández Acosta, Francisco
Cruz-Haces, Marcela
Löppönen, Heikki
Mackay-Sim, Alan
Kaikkonen, Minna U.
Koivisto, Anne M.
Malm, Tarja
White, Anthony R.
Giugno, Rosalba
Chew, Sweelin
Kanninen, Katja M.
author_facet Lampinen, Riikka
Fazaludeen, Mohammad Feroze
Avesani, Simone
Örd, Tiit
Penttilä, Elina
Lehtola, Juha-Matti
Saari, Toni
Hannonen, Sanna
Saveleva, Liudmila
Kaartinen, Emma
Fernández Acosta, Francisco
Cruz-Haces, Marcela
Löppönen, Heikki
Mackay-Sim, Alan
Kaikkonen, Minna U.
Koivisto, Anne M.
Malm, Tarja
White, Anthony R.
Giugno, Rosalba
Chew, Sweelin
Kanninen, Katja M.
author_sort Lampinen, Riikka
collection PubMed
description 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.
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spelling pubmed-88701602022-02-25 Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease Patients Lampinen, Riikka Fazaludeen, Mohammad Feroze Avesani, Simone Örd, Tiit Penttilä, Elina Lehtola, Juha-Matti Saari, Toni Hannonen, Sanna Saveleva, Liudmila Kaartinen, Emma Fernández Acosta, Francisco Cruz-Haces, Marcela Löppönen, Heikki Mackay-Sim, Alan Kaikkonen, Minna U. Koivisto, Anne M. Malm, Tarja White, Anthony R. Giugno, Rosalba Chew, Sweelin Kanninen, Katja M. Cells Article 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. MDPI 2022-02-15 /pmc/articles/PMC8870160/ /pubmed/35203328 http://dx.doi.org/10.3390/cells11040676 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lampinen, Riikka
Fazaludeen, Mohammad Feroze
Avesani, Simone
Örd, Tiit
Penttilä, Elina
Lehtola, Juha-Matti
Saari, Toni
Hannonen, Sanna
Saveleva, Liudmila
Kaartinen, Emma
Fernández Acosta, Francisco
Cruz-Haces, Marcela
Löppönen, Heikki
Mackay-Sim, Alan
Kaikkonen, Minna U.
Koivisto, Anne M.
Malm, Tarja
White, Anthony R.
Giugno, Rosalba
Chew, Sweelin
Kanninen, Katja M.
Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease Patients
title Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease Patients
title_full Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease Patients
title_fullStr Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease Patients
title_full_unstemmed Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease Patients
title_short Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease Patients
title_sort single-cell rna-seq analysis of olfactory mucosal cells of alzheimer’s disease patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870160/
https://www.ncbi.nlm.nih.gov/pubmed/35203328
http://dx.doi.org/10.3390/cells11040676
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