Details

Autor(en) / Beteiligte

• Friedman, Brad A.
• Srinivasan, Karpagam
• Ayalon, Gai
• Meilandt, William J.
• Lin, Han
• Huntley, Melanie A.
• Cao, Yi
• Lee, Seung-Hye
• Haddick, Patrick C.G.
• Ngu, Hai
• Modrusan, Zora
• Larson, Jessica L.
• Kaminker, Joshua S.
• van der Brug, Marcel P.
• Hansen, David V.

Titel

Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer’s Disease Not Evident in Mouse Models

Ist Teil von

• Cell reports (Cambridge), 2018-01, Vol.22 (3), p.832-847

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer’s disease (AD) model, we identified microglial subsets—distinct from previously reported “disease-associated microglia”—expressing interferon-related or proliferation modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative diseases, including a new AD dataset. Correcting for altered cellular composition of AD tissue, we observed elevated expression of the neurodegeneration-related modules, but also modules not implicated using expression profiles from mouse models alone. We provide a searchable, interactive database for exploring gene expression in all these datasets (http://research-pub.gene.com/BrainMyeloidLandscape). Understanding the dimensions of CNS myeloid cell activation in human disease may reveal opportunities for therapeutic intervention. [Display omitted] •Meta-analysis of purified mouse CNS myeloid cell profiles from 69 different conditions•7 co-regulated gene sets include one enriched in neurodegenerative disease models•Distinct classes of activated microglia identified in Alzheimer’s mouse model•Resources for further exploration: comprehensive Excel tables and interactive website Ready to move beyond M1 and M2? In this meta-analysis of CNS myeloid cell expression profiles, Friedman et al. identify gene modules associated with diverse microglial activation states. These modules identify distinct subsets of microglia in an Alzheimer’s model and reveal aspects of the human disease not apparent in mouse models.