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 involves a pro-inflammatory cytokine/chemokine cytokine response microglia or CRM re

SUBMITTER: Mancuso R 

PROVIDER: S-EPMC11089003 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature