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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-8870160 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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