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Cited by 281Neuroinflammation and Neurodegeneration MechanismsSingle-cell and spatial transcriptomicsMultiple Sclerosis Research Studies

Single‐cell transcriptomics reveals distinct inflammation‐induced microglia signatures

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Sousa, Carole, Golebiewska, Anna, Poovathingal, Suresh K, Kaoma, Tony, Pires‐Afonso, Yolanda, Martina, Silvia, Coowar, Djalil, Azuaje, Francisco +5 more·2018·The EMBO Reports
DOI 10.15252/embr.201846171PMC PMC6216255
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Abstract

Microglia are specialized parenchymal‐resident phagocytes of the central nervous system (CNS) that actively support, defend and modulate the neural environment. Dysfunctional microglial responses are thought to worsen CNS diseases; nevertheless, their impact during neuroinflammatory processes remains largely obscure. Here, using a combination of single‐cell RNA sequencing and multicolour flow cytometry, we comprehensively profile microglia in the brain of lipopolysaccharide (LPS)‐injected mice. By excluding the contribution of other immune CNS‐resident and peripheral cells, we show that microglia isolated from LPS‐injected mice display a global downregulation of their homeostatic signature together with an upregulation of inflammatory genes. Notably, we identify distinct microglial activated profiles under inflammatory conditions, which greatly differ from neurodegenerative disease‐associated profiles. These results provide insights into microglial heterogeneity and establish a resource for the identification of specific phenotypes in CNS disorders, such as neuroinflammatory and neurodegenerative diseases.

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  • Compared to APOE2, APOE4 had significant upregulation of several DAM marker genes (Cd74, Cst7, Cd63, Cd9, Ccl6), complement cascade genes (C1qa, C1qb, C1qc), and the pro-inflammatory gene Nfkbia.

    “We observed that compared to APOE2, APOE4 had a significant upregulation of several DAM marker genes such as Cd74, Cst7, Cd63, Cd9, Ccl6, complement cascade genes (C1qa, C1qb, C1qc) and the pro-inflammatory gene Nfkbia (Sousa et al, 2018).”

    From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Sousa et al, 2018

    In Results and Discussion (page unavailable), Sousa et al. compare inflammatory microglia with DAM, identify Cd9 as a disease-associated gene, and identify C1qa, C1qb, and C1qc as complement-system genes. The paper does not report the citing authors’ APOE4-versus-APOE2 result or establish the full listed set as DAM markers; it instead reports that those complement genes were downregulated in DAM relative to controls. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • At transcriptional level, microglia from the APOE4 group upregulated several DAM markers (Cd74, Cst7, Cd63, Cd9, Ccl6), complement cascade genes (C1qa, C1qb, C1qc) and the pro-inflammatory gene Nfkbia, similar to transcriptomic changes in microglia from APOE4 AD individuals.

    “At transcriptional level, microglia from the APOE4 group upregulated several DAM markers (Cd74, Cst7, Cd63, Cd9, Ccl6), complement cascade genes (C1qa, C1qb, C1qc) and the pro-inflammatory gene Nfkbia (Sousa et al, 2018), similar to transcriptomic changes in microglia from APOE4 AD individuals (Serrano-Pozo et al, 2021).”

    From APOE from astrocytes restores Alzheimer’s Aβ-pathology and DAM-like responses in APOE deficient microglia (2024) · cites this paper as Sousa et al, 2018

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Authors
Sousa, C., Golebiewska, A., Poovathingal, S. K., Kaoma, T., Pires‐Afonso, Y., Martina, S., Coowar, D., Azuaje, F., Skupin, A., Balling, R., Biber, K., Niclou, S. P., & Michelucci, A.
Affiliations
  • University of Luxembourg (LU)
  • Luxembourg Institute of Health (LU)
  • University Medical Center Groningen (NL)
Corresponding author
Michelucci, Alessandro
ORCID
Venue
The EMBO Reports
Publisher
Springer Science and Business Media LLC
Published
2018-09-11
Volume
19
Issue
11
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
DOI
10.15252/embr.201846171
PMC
PMC6216255
OpenAlex
W2891901614
Cited by
281
References
19
Citations by year
2026: 22 · 2025: 33 · 2024: 46 · 2023: 45 · 2022: 45 · 2021: 42 · 2020: 28 · 2019: 20
FWCI
9.88
Type
journal article
Language
en
Open access
Licence
Locations
  • EMBO Reports (publishedVersion, other-oa)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, other-oa)
  • Open Repository and Bibliography (University of Luxembourg) (submittedVersion, cc-by-nc-sa)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc-nd)
Funders
  • Fondation du Pélican de Mie et Pierre Hippert‐Faber Under the Aegis of Fondation de Luxembourg
  • National Biomedical Computation Resource (C14/BM/7975668/CaSCAD)
  • Luxembourg Institute of Health
  • Luxembourg Centre for Systems Biomedicine
  • Fonds National de la Recherche Luxembourg (6916713, PRIDE15/10675146, PRIDE16/10907093)
  • HHS | National Institutes of Health (P41 GM103426)
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, neuroinflammation, lipopolysaccharide, microglial heterogeneity, microglial activation, neurodegenerative diseases, single-cell transcriptomics
MeSH terms
Animals, Encephalitis, Female, Flow Cytometry, Gene Expression Regulation, Homeostasis, Inflammation, Lipopolysaccharides, Male, Mice, Inbred C57BL, Sequence Analysis, RNA, Leukocyte Common Antigens, Microglia, Neurodegenerative Diseases, CD11b Antigen, Single-Cell Analysis

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