The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution
Open accessAbstract
Microglia have critical roles not only in neural development and homeostasis, but also in neurodegenerative and neuroinflammatory diseases of the central nervous system 1-4. These highly diverse and specialized functions may be executed by subsets of microglia that already exist in situ, or by specific subsets of microglia that develop from a homogeneous pool of cells on demand. However, little is known about the presence of spatially and temporally restricted subclasses of microglia in the central nervous system during development or disease. Here we combine massively parallel single-cell analysis, single-molecule fluorescence in situ hybridization, advanced immunohistochemistry and computational modelling to comprehensively characterize subclasses of microglia in multiple regions of the central nervous system during development and disease. Single-cell analysis of tissues of the central nervous system during homeostasis in mice revealed specific time- and region-dependent subtypes of microglia. Demyelinating and neurodegenerative diseases evoked context-dependent subtypes of microglia with distinct molecular hallmarks and diverse cellular kinetics. Corresponding clusters of microglia were also identified in healthy human brains, and the brains of patients with multiple sclerosis. Our data provide insights into the endogenous immune system of the central nervous system during development, homeostasis and disease, and may also provide new targets for the treatment of neurodegenerative and neuroinflammatory pathologies.
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“The two predominant modules for MG4 were ‘MS-associated’23 and ‘MIMS-foamy’25 (Fig. 5C).”
From CHIT1 at diagnosis predicts faster disability progression and reflects early microglial activation in multiple sclerosis (2024) · cites this paper as [23]
In the citing paper
“Genetic association studies have demonstrated the critical involvement of the microglial immune response in Alzheimer's disease (AD) pathogenesis.”
From Genetic variants of phospholipase C-γ2 alter the phenotype and function of microglia and confer differential risk for Alzheimer’s disease (2023) · cites this paper as [2]
In the citing paper
“A concerted effort to identify genes that confer altered risk for Alzheimer's disease (AD) is leading to the recognition that many disease-risk genes are associated with the microgliamediated immune response in the AD brain 1-3 .”
From Genetic variants of phospholipase C-γ2 alter the phenotype and function of microglia and confer differential risk for Alzheimer’s disease (2023) · cites this paper as [2]
In the citing paper
“Padi2 is enriched in subsets of microglia isolated from human MS tissue”
From Mouse microglia express unique miRNA-mRNA networks to facilitate age-specific functions in the developing central nervous system (2023) · cites this paper as [19]
In the citing paper
“Microglia are highly dynamic cells that are strongly influenced by different environmental signals which result in distinct phenotypes and functions across brain regions4–9.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [9]
In the citing paper
“Regional and age-related differences in microglial density, morphology, gene, and protein expression have previously been described for both animals and humans5,6,9,60,61.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [9]
In the citing paper
“There are several methodological differences (recruitment of tissue, studied brain region, postmortem delay, pH, age, diagnosis, medication use) that could interfere with the interpretation of comparisons between MiGA and other microglial datasets5,9,42.”
From Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies (2022) · cites this paper as [9]
In the citing paper
“These studies have largely concluded that microglia undergo the most prominent changes in diseased brains, due to a combination of increased microglia numbers along with a robust transcriptional activation signature on a per-microglia basis.”
From Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease (2020) · cites this paper as [9]
In the citing paper
“Single-cell transcriptomic studies reveal a relatively homogeneous adult microglia population, and greater heterogeneity of microglia states at different developmental stages, during aging and in pathological conditions (Hammond et al., 2019; Li et al., 2019; Masuda et al., 2019).”
From What is a cell type and how to define it? (2022) · cites this paper as Masuda et al., 2019
In the citing paper
“sc/snRNA-seq also provides insight into the diversity of glial cells including the oligodendrocyte lineage (Marques et al., 2016) and functional states of microglia (Masuda et al., 2019).”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Masuda et al., 2019
Citations
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Gu, Z., Eils, R., & Schlesner, M. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw313 · Cited by 10,037
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493
The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote
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Microglia Function in the Central Nervous System During Health and Neurodegeneration
Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894
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Metadata
- Authors
- Masuda, T., Sankowski, R., Staszewski, O., Böttcher, C., Amann, L., Sagar, Scheiwe, C., Nessler, S., Kunz, P., van Loo, G., Coenen, V. A., Reinacher, P. C., Michel, A., Sure, U., Gold, R., Grün, D., Priller, J., Stadelmann, C., & Prinz, M.
- Affiliations
- University of Freiburg (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- Universitätsmedizin Göttingen (DE)
- Essen University Hospital (DE)
- St. Josef-Hospital (DE)
- German Center for Neurodegenerative Diseases (DE)
- Corresponding author
- Prinz, Marco
- ORCID
- Venue
- Nature
- Published
- 2019-02
- Volume
- 566
- Issue
- 7744
- Pages
- 388-392
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2914756534
- Cited by
- 1,310
- References
- 37
- Citations by year
- 2026: 136 · 2025: 145 · 2024: 187 · 2023: 184 · 2022: 207 · 2021: 209 · 2020: 169 · 2019: 71
- FWCI
- 72.26
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-03-27)
- Open access
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- DZNE Pub (submittedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- National Multiple Sclerosis Society
- Deutsche Forschungsgemeinschaft (SFB-1160, SFB 992, SFB/ TRR 167, TRR 167)
- Bundesministerium für Bildung und Forschung
- Karolinska Institutet
- Deutschen Multiple Sklerose Gesellschaft
- Kanae Foundation for the Promotion of Medical Science
- Roman, Marga und Mareille Sobek Stiftung
- Medical Research Council (MC_PC_16031)
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- microglia, microglial heterogeneity, microglial subtypes, central nervous system development, neuroinflammation, neurodegenerative diseases, demyelination, multiple sclerosis, mouse brain, human brain, single-cell transcriptomics, single-molecule fluorescence in situ hybridization, brain homeostasis
- MeSH terms
- Animals, Brain, Cell Separation, Demyelinating Diseases, Female, Humans, Kinetics, Male, Multiple Sclerosis, Case-Control Studies, Microglia, Neurodegenerative Diseases, Mice, Single-Cell Analysis, Spatio-Temporal Analysis
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