Human induced pluripotent stem cell-derived microglia with a CX3CR1-V249I genetic variant exhibit dysfunctional phenotypes and modulate neuronal growth and function.

ABSTRACT: The involvement of microglia in neurodegenerative diseases has drawn increasing attention, as many genetic risk factors are preferentially expressed in microglia. Microglial fractalkine receptor (CX3CR1) signaling regulates many key microglial functions, and the CX3CR1-V249I single nucleotide polymorphism (SNP) has been associated with increased risk for multiple neurodegenerative conditions, including Alzheimer's disease, yet its functional consequences in human microglia remain unexplored. In this study, we generated iPSC-derived human microglia-like cells (hMGLs) and found that the CX3CR1-V249I variant increased susceptibility to starvation-induced cell death, reduced amyloid-beta uptake, altered microglial morphology, and impaired migration, with more pronounced effects in homozygous c

SUBMITTER: Tutrow KD 

PROVIDER: S-EPMC12236714 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature