Cited by 449Neuroinflammation and Neurodegeneration MechanismsSingle-cell and spatial transcriptomicsMultiple Sclerosis Research Studies

Mapping microglia states in the human brain through the integration of high-dimensional techniques

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Sankowski, Roman, Böttcher, Chotima, Masuda, Takahiro, Geirsdottir, Laufey, Sagar, Sindram, Elena, Seredenina, Tamara, Muhs, Andreas +7 more·2019·Nature Neuroscience

Abstract

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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Crossref · 10.1038/s41593-019-0532-y

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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.”

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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
Venue
Nature Neuroscience
Published
2019-11-18
Volume
22
Issue
12
Pages
2098-2110
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W2987759842
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
Open access
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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