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Spatial proteomics reveals human microglial states shaped by anatomy and neuropathology.
Mrdjen, Dunja; Amouzgar, Meelad; Cannon, Bryan; Liu, Candace; Spence, Angie; McCaffrey, Erin; Bharadwaj, Anusha; Tebaykin, Dmitry; Bukhari, Syed; Hartmann, Felix J; Kagel, Adam; Vijayaragavan, Kausalia; Oliveria, John Paul; Yakabi, Koya; Serrano, Geidy E; Corrada, Maria M; Kawas, Claudia H; Camacho, Christine; Bosse, Marc; Tibshirani, Robert; Beach, Thomas G; Angelo, Michael; Montine, Thomas; Bendall, Sean C.
Affiliation
  • Mrdjen D; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Amouzgar M; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Cannon B; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Liu C; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Spence A; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • McCaffrey E; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Bharadwaj A; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Tebaykin D; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Bukhari S; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Hartmann FJ; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Kagel A; Systems Immunology and Single-Cell Biology, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
  • Vijayaragavan K; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Oliveria JP; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Yakabi K; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Serrano GE; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Corrada MM; Banner Sun Health Research Institute, Sun City, 85351, AZ, USA.
  • Kawas CH; Department of Neurology, University of California, Irvine, 9269, CA, USA.
  • Camacho C; Department of Neurology, University of California, Irvine, 9269, CA, USA.
  • Bosse M; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Tibshirani R; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Beach TG; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Angelo M; Banner Sun Health Research Institute, Sun City, 85351, AZ, USA.
  • Montine T; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
  • Bendall SC; Department of Pathology, Stanford University, School of Medicine, Palo Alto 94304, CA, USA.
Res Sq ; 2023 Jun 02.
Article in En | MEDLINE | ID: mdl-37398389
ABSTRACT
Microglia are implicated in aging, neurodegeneration, and Alzheimer's disease (AD). Traditional, low-plex, imaging methods fall short of capturing in situ cellular states and interactions in the human brain. We utilized Multiplexed Ion Beam Imaging (MIBI) and data-driven analysis to spatially map proteomic cellular states and niches in healthy human brain, identifying a spectrum of microglial profiles, called the microglial state continuum (MSC). The MSC ranged from senescent-like to active proteomic states that were skewed across large brain regions and compartmentalized locally according to their immediate microenvironment. While more active microglial states were proximal to amyloid plaques, globally, microglia significantly shifted towards a, presumably, dysfunctional low MSC in the AD hippocampus, as confirmed in an independent cohort (n=26). This provides an in situ single cell framework for mapping human microglial states along a continuous, shifting existence that is differentially enriched between healthy brain regions and disease, reinforcing differential microglial functions overall.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Res Sq Year: 2023 Document type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Res Sq Year: 2023 Document type: Article Affiliation country: United States