Mapping microglia states in the human brain through the integration of high-dimensional techniques
Open accessAbstract
Microglia are tissue-resident macrophages of the CNS that orchestrate local immune responses and contribute to several neurological and psychiatric diseases. Little is known about human microglia and how they orchestrate their highly plastic, context-specific adaptive responses during pathology. Here we combined two high-dimensional technologies, single-cell RNA-sequencing and time-of-flight mass cytometry, to identify microglia states in the human brain during homeostasis and disease. This approach enabled us to identify and characterize a previously unappreciated spectrum of transcriptional states in human microglia. These transcriptional states are determined by their spatial distribution, and they further change with aging and brain tumor pathology. This description of multiple microglia phenotypes in the human CNS may open promising new avenues for subset-specific therapeutic interventions.
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The inhibitor-based protocol offers greater experimental and tissue-/cell-type flexibility than previously developed experimental and computational solutions.
“Our inhibitor-based protocol offers much greater experimental and tissue-/cell-type flexibility than previously developed experimental and computational solutions for this pervasive issue (see additional discussion of some alternative methods in Supplementary Note 7)33,34,45,65,67,68.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [67]
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- Authors
- Sankowski, R., Böttcher, C., Masuda, T., Geirsdottir, L., Sagar, Sindram, E., Seredenina, T., Muhs, A., Scheiwe, C., Shah, M. J., Heiland, D. H., Schnell, O., Grün, D., Priller, J., & Prinz, M.
- Affiliations
- University of Freiburg (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- AC Immune (Switzerland) (CH)
- UK Dementia Research Institute (GB)
- Corresponding author
- Grün, Dominic
- Priller, Josef
- Prinz, Marco
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2019-11-18
- Volume
- 22
- Issue
- 12
- Pages
- 2098-2110
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2987759842
- Semantic Scholar
- 8103efba60e0c30f946a400e4e7d0052ecb66465
- Cited by
- 449
- References
- 66
- Citations by year
- 2026: 44 · 2025: 53 · 2024: 69 · 2023: 64 · 2022: 78 · 2021: 86 · 2020: 54 · 2019: 1
- FWCI
- 24.10
- Type
- journal article
- Language
- en
- Update notices
- correction (2022-05-30)
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- DZNE Pub (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Medical Research Council (MC_PC_16031)
- 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 › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- microglia, human brain, microglial phenotype, transcriptional states, single-cell RNA sequencing, mass cytometry, brain aging, glioblastoma, neuroinflammation, CNS immune response
- MeSH terms
- Adolescent, Adult, Aged, Aging, Brain, Female, Flow Cytometry, Glioblastoma, Humans, Immunohistochemistry, Male, Middle Aged, Transcription, Genetic, Sequence Analysis, RNA, Microglia, Young Adult
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