Xenografted human microglia display diverse transcriptomic states in response to Alzheimer’s disease-related amyloid-β pathology

Abstract Microglia are central players in Alzheimer’s disease pathology but analyzing microglial states in human brain samples is challenging due to genetic diversity, postmortem delay and admixture of pathologies. To circumvent these issues, here we generated 138,577 single-cell expression profiles of human stem cell-derived microglia xenotransplanted in the brain of the App NL-G-F model of amyloid pathology and wild-type controls. Xenografted human microglia adopt a disease-associated profile similar to that seen in mouse microglia, but display a more pronounced human leukocyte antigen or HLA state, likely related to antigen presentation in response to amyloid plaques. The human microglial response also…

• AA
  Alzheimer's Association

  Award: AARF-20-684397
• BF
  BrightFocus Foundation
• UR
  UK Research and Innovation

  Award: MR/Y014847/1
• QE
  Queen Elisabeth Medical Foundation
• EC
  European Commission

  Awards: 101041867, ERC-834682 CELLPHASE_AD, 834682, 2022-2025
• FW
  Fonds Wetenschappelijk Onderzoek

  Awards: G0C9219N, G0K9422N, 1122423N, 12ZX621N, 1139520N, S001221N
• KL
  KU Leuven
• VI
  Vlaams Instituut voor Biotechnologie
• UA
  Universiteit Antwerpen

  Award: FFB210307
• VR
  Vlaamse regering
• UD
  UK Dementia Research Institute
• FP
  Fondation pour la Recherche sur Alzheimer
• H2
  Horizon 2020 Framework Programme
• MR
  Medical Research Council

  Awards: MR/Y014847/1, MR/Y014847/1
• HM
  H2020 Marie Skłodowska-Curie Actions

  Award: Horizon 2020