Single-nucleus RNA-seq is not suitable for detection of microglial activation genes in humans
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Nicola Thrupp Carlo Sala Frigerio Leen Wolfs Nathan G Skene Nicola Fattorelli Suresh Poovathingal Yannick Fourne Paul M Matthews Tom Theys Renzo Mancuso Bart De Strooper Mark FiersAbstract
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.
Journal details
Journal Cell Reports
Volume 32
Issue number 13
Pages 108189
Available online
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Full text links
Publisher website (DOI) 10.1016/j.celrep.2020.108189
Europe PubMed Central 32997994
Pubmed 32997994
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