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Alzheimer’s disease alters the transcriptomic profile of natural killer cells at single-cell resolution

Alzheimer’s disease (AD) is the most common dementia without an effective cure at least partially due to incomplete understanding of the disease. Inflammation has emerged as a central player in the onset and progression of AD. As innate lymphoid cells, natural killer (NK) cells orchestrate the initi...

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Autores principales: Qi, Caiyun, Liu, Fang, Zhang, Wenjun, Han, Yali, Zhang, Nan, Liu, Qiang, Li, Handong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9666759/
https://www.ncbi.nlm.nih.gov/pubmed/36405736
http://dx.doi.org/10.3389/fimmu.2022.1004885
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author Qi, Caiyun
Liu, Fang
Zhang, Wenjun
Han, Yali
Zhang, Nan
Liu, Qiang
Li, Handong
author_facet Qi, Caiyun
Liu, Fang
Zhang, Wenjun
Han, Yali
Zhang, Nan
Liu, Qiang
Li, Handong
author_sort Qi, Caiyun
collection PubMed
description Alzheimer’s disease (AD) is the most common dementia without an effective cure at least partially due to incomplete understanding of the disease. Inflammation has emerged as a central player in the onset and progression of AD. As innate lymphoid cells, natural killer (NK) cells orchestrate the initiation and evolution of inflammatory responses. Yet, the transcriptomic features of NK cells in AD remain poorly understood. We assessed the diversity of NK cells using web-based single-cell RNA sequencing data of blood NK cells from patients with AD and control subjects and flow cytometry. We identified a contraction of NK cell compartment in AD, accompanied by a reduction of cytotoxicity. Unbiased clustering revealed four subsets of NK cells in AD, i.e., CD56(bright) NK cells, CD56(dim) effector NK cells, adaptive NK cells, and a unique NK cell subset that is expanded and characterized by upregulation of CX3CR1, TBX21, MYOM2, DUSP1, and ZFP36L2, and negatively correlated with cognitive function in AD patients. Pseudo-temporal analysis revealed that this unique NK cell subset was at a late stage of NK cell development and enriched with transcription factors TBX21, NFATC2, and SMAD3. Together, our study identified a distinct NK cell subset and its potential involvement in AD.
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spelling pubmed-96667592022-11-17 Alzheimer’s disease alters the transcriptomic profile of natural killer cells at single-cell resolution Qi, Caiyun Liu, Fang Zhang, Wenjun Han, Yali Zhang, Nan Liu, Qiang Li, Handong Front Immunol Immunology Alzheimer’s disease (AD) is the most common dementia without an effective cure at least partially due to incomplete understanding of the disease. Inflammation has emerged as a central player in the onset and progression of AD. As innate lymphoid cells, natural killer (NK) cells orchestrate the initiation and evolution of inflammatory responses. Yet, the transcriptomic features of NK cells in AD remain poorly understood. We assessed the diversity of NK cells using web-based single-cell RNA sequencing data of blood NK cells from patients with AD and control subjects and flow cytometry. We identified a contraction of NK cell compartment in AD, accompanied by a reduction of cytotoxicity. Unbiased clustering revealed four subsets of NK cells in AD, i.e., CD56(bright) NK cells, CD56(dim) effector NK cells, adaptive NK cells, and a unique NK cell subset that is expanded and characterized by upregulation of CX3CR1, TBX21, MYOM2, DUSP1, and ZFP36L2, and negatively correlated with cognitive function in AD patients. Pseudo-temporal analysis revealed that this unique NK cell subset was at a late stage of NK cell development and enriched with transcription factors TBX21, NFATC2, and SMAD3. Together, our study identified a distinct NK cell subset and its potential involvement in AD. Frontiers Media S.A. 2022-11-02 /pmc/articles/PMC9666759/ /pubmed/36405736 http://dx.doi.org/10.3389/fimmu.2022.1004885 Text en Copyright © 2022 Qi, Liu, Zhang, Han, Zhang, Liu and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Qi, Caiyun
Liu, Fang
Zhang, Wenjun
Han, Yali
Zhang, Nan
Liu, Qiang
Li, Handong
Alzheimer’s disease alters the transcriptomic profile of natural killer cells at single-cell resolution
title Alzheimer’s disease alters the transcriptomic profile of natural killer cells at single-cell resolution
title_full Alzheimer’s disease alters the transcriptomic profile of natural killer cells at single-cell resolution
title_fullStr Alzheimer’s disease alters the transcriptomic profile of natural killer cells at single-cell resolution
title_full_unstemmed Alzheimer’s disease alters the transcriptomic profile of natural killer cells at single-cell resolution
title_short Alzheimer’s disease alters the transcriptomic profile of natural killer cells at single-cell resolution
title_sort alzheimer’s disease alters the transcriptomic profile of natural killer cells at single-cell resolution
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9666759/
https://www.ncbi.nlm.nih.gov/pubmed/36405736
http://dx.doi.org/10.3389/fimmu.2022.1004885
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