Amelioration of signaling deficits underlying metabolic shortfall in TREM2^R47H human iPSC-derived microglia.

ABSTRACT: The microglial triggering receptor expressed on myeloid cells 2 (TREM2) is required for diverse microglia responses in neurodegeneration, including immunometabolic plasticity, phagocytosis, and survival. We previously identified that patient iPSC-derived microglia (iPS-Mg) harboring the Alzheimer's disease (AD) TREM2^R47H hypomorph display several functional deficits linked to metabolism. To investigate whether these deficits are associated with disruptions in metabolite signaling, we generated common variant, TREM2^R47H and TREM2^-/- variant human iPS-Mg. We assessed the ability of supplementation with citrate or succinate, key metabolites and cell cycle breaking points upon microglia activation, to overcome these functional deficits with potential impact on

SUBMITTER: Vasilopoulou F 

PROVIDER: S-EPMC11970715 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature