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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MDPI AG
2022-02-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/4/676 |
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| author | Riikka Lampinen Mohammad Feroze Fazaludeen Simone Avesani Tiit Örd Elina Penttilä Juha-Matti Lehtola Toni Saari Sanna Hannonen Liudmila Saveleva Emma Kaartinen Francisco Fernández Acosta Marcela Cruz-Haces Heikki Löppönen Alan Mackay-Sim Minna U. Kaikkonen Anne M. Koivisto Tarja Malm Anthony R. White Rosalba Giugno Sweelin Chew Katja M. Kanninen |
| author_facet | Riikka Lampinen Mohammad Feroze Fazaludeen Simone Avesani Tiit Örd Elina Penttilä Juha-Matti Lehtola Toni Saari Sanna Hannonen Liudmila Saveleva Emma Kaartinen Francisco Fernández Acosta Marcela Cruz-Haces Heikki Löppönen Alan Mackay-Sim Minna U. Kaikkonen Anne M. Koivisto Tarja Malm Anthony R. White Rosalba Giugno Sweelin Chew Katja M. Kanninen |
| author_sort | Riikka Lampinen |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T22:20:43Z |
| format | Article |
| id | doaj.art-f37964f4ad0445378ce4d9197ff96e19 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T22:20:43Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f37964f4ad0445378ce4d9197ff96e192023-11-23T19:15:13ZengMDPI AGCells2073-44092022-02-0111467610.3390/cells11040676Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease PatientsRiikka Lampinen0Mohammad Feroze Fazaludeen1Simone Avesani2Tiit Örd3Elina Penttilä4Juha-Matti Lehtola5Toni Saari6Sanna Hannonen7Liudmila Saveleva8Emma Kaartinen9Francisco Fernández Acosta10Marcela Cruz-Haces11Heikki Löppönen12Alan Mackay-Sim13Minna U. Kaikkonen14Anne M. Koivisto15Tarja Malm16Anthony R. White17Rosalba Giugno18Sweelin Chew19Katja M. Kanninen20A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandDepartment of Computer Science, University of Verona, 37134 Verona, ItalyA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandDepartment of Otorhinolaryngology, University of Eastern Finland, Kuopio University Hospital, 70210 Kuopio, FinlandBrain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, FinlandBrain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, FinlandBrain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandDepartment of Otorhinolaryngology, University of Eastern Finland, Kuopio University Hospital, 70210 Kuopio, FinlandGriffith Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, AustraliaA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandBrain Research Unit, Department of Neurology, School of Medicine, University of Eastern Finland, 70210 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandDepartment of Cell and Molecular Biology, QIMR Berghofer, Medical Research Institute, Mental Health Program, Herston, QLD 4006, AustraliaDepartment of Computer Science, University of Verona, 37134 Verona, ItalyA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, FinlandOlfaction 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.https://www.mdpi.com/2073-4409/11/4/676Alzheimer’s diseaseolfactory mucosaamyloid betasingle-cell RNA-sequencingmitochondria |
| spellingShingle | Riikka Lampinen Mohammad Feroze Fazaludeen Simone Avesani Tiit Örd Elina Penttilä Juha-Matti Lehtola Toni Saari Sanna Hannonen Liudmila Saveleva Emma Kaartinen Francisco Fernández Acosta Marcela Cruz-Haces Heikki Löppönen Alan Mackay-Sim Minna U. Kaikkonen Anne M. Koivisto Tarja Malm Anthony R. White Rosalba Giugno Sweelin Chew Katja M. Kanninen Single-Cell RNA-Seq Analysis of Olfactory Mucosal Cells of Alzheimer’s Disease Patients Cells Alzheimer’s disease olfactory mucosa amyloid beta single-cell RNA-sequencing mitochondria |
| 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 | Alzheimer’s disease olfactory mucosa amyloid beta single-cell RNA-sequencing mitochondria |
| url | https://www.mdpi.com/2073-4409/11/4/676 |
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