ArticleNature neuroscience2022
Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain.
Article in Nature neuroscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 262 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
262 citing papers in PubMed, 420 citations in OpenAlex.
- Leveraging Single-Cell RNA Sequencing to Characterize Murine Ewing Sarcoma Xenografts.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Microglia activation by derepression of endogenous retroviruses drives inflammation and cellular senescence.Nature neuroscience · 2026Article
- Microglial states revisited: from homeostasis to disease.Nature reviews. Neuroscience · 2026Review
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- Single-nucleus transcriptomics reveals cell type-specific remodeling and epilepsy-associated microglia.iScience · 2026Article
- Isolation of Brain Microglia to Study Persistence of Human Immunodeficiency Virus-1.Journal of visualized experiments : JoVE · 2026Article
- Review
- A Conserved Macrophage-to-Hepatic Stellate Cell PDGF Axis in Human MASH Identified by Multi-Cohort sc/snRNA-Seq Re-Analysis.International journal of molecular sciences · 2026Article
- Priming of CD8Nature neuroscience · 2026Article
- Single-cell transcriptomics of human brain disorders.Molecular psychiatry · 2026Review
- Article
- Plasticity of human microglia and brain perivascular macrophages in aging and Alzheimer's disease.Nature genetics · 2026Article
- Circadian rhythms in microglia mediate early life synaptic development in a sex-specific manner.Cell reports · 2026Article
- Th17 effector cytokines induce shared and distinct microglial and endothelial cell responses in a mouse model for post-streptococcal encephalitis.Nature communications · 2026Article
- Activity-dependent protein synthesis in neurons requires microglial-metabolic coupling.Cell metabolism · 2026Article
- Astrocyte heterogeneity in brain metastases.Molecular oncology · 2026Review
- Microbiota-Driven microglia reprogramming reverses depressive-like behaviors through Peripheral-to-Central immune crosstalk.Molecular psychiatry · 2026Article
- Longitudinal analysis reveals myeloid cell contributions to murine neuroPASC pathogenesis.Nature communications · 2026Article
- cellGeometry: ultra-fast single-cell deconvolution of bulk RNA-Seq using a geometric solution.Nature communications · 2026Article
- The Clearance-Centered Bottleneck in Alzheimer's Disease: From Coupled Glymphatic-Lymphatic Circuits to Therapeutic Opportunities.Molecular neurobiology · 2026Review
202 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
23 authors at 7 institutions in 2 countries.
Funding
Abstract
A key aspect of nearly all single-cell sequencing experiments is dissociation of intact tissues into single-cell suspensions. While many protocols have been optimized for optimal cell yield, they have often overlooked the effects that dissociation can have on ex vivo gene expression. Here, we demonstrate that use of enzymatic dissociation on brain tissue induces an aberrant ex vivo gene expression signature, most prominently in microglia, which is prevalent in published literature and can substantially confound downstream analyses. To address this issue, we present a rigorously validated protocol that preserves both in vivo transcriptional profiles and cell-type diversity and yield across tissue types and species. We also identify a similar signature in postmortem human brain single-nucleus RNA-sequencing datasets, and show that this signature is induced in freshly isolated human tissue by exposure to elevated temperatures ex vivo. Together, our results provide a methodological solution for preventing artifactual gene expression changes during fresh tissue digestion and a reference for future deeper analysis of the potential confounding states present in postmortem human samples.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.