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Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans

Thrupp, N; Sala Frigerio, C; Wolfs, L; Skene, NG; Fattorelli, N; Poovathingal, S; Fourne, Y; ... Fiers, M; + view all (2020) Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans. Cell Reports , 32 (13) , Article 108189. 10.1016/j.celrep.2020.108189. Green open access

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Abstract

Single-nucleus RNA sequencing (snRNA-seq) is used as an alternative to single-cell RNA-seq, as it allows transcriptomic profiling of frozen tissue. However, it is unclear whether snRNA-seq is able to detect cellular state in human tissue. Indeed, snRNA-seq analyses of human brain samples have failed to detect a consistent microglial activation signature in Alzheimer's disease. Our comparison of microglia from single cells and single nuclei of four human subjects reveals that, although most genes show similar relative abundances in cells and nuclei, a small population of genes (∼1%) is depleted in nuclei compared to whole cells. This population is enriched for genes previously implicated in microglial activation, including APOE, CST3, SPP1, and CD74, comprising 18% of previously identified microglial-disease-associated genes. Given the low sensitivity of snRNA-seq to detect many activation genes, we conclude that snRNA-seq is not suited for detecting cellular activation in microglia in human disease.

Type: Article
Title: Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2020.108189
Publisher version: https://doi.org/10.1016/j.celrep.2020.108189
Language: English
Additional information: © 2020 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: ARM, Alzheimer’s disease, activation, microglia, microglial activation, single-cell RNA-seq, single-nucleus RNA-seq
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UK Dementia Research Institute HQ
URI: https://discovery.ucl.ac.uk/id/eprint/10111373
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