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Figure 1. Microglia and human pluripotent stem cells. Microglia are increasingly emerging as potential drivers of CNS diseases. Using high-throughput sequencing techniques such as GWAS and multi-omics analysis, a series of risk genes/loci associated with neurodegenerative diseases have been detected selectively or preferentially in microglia rather than other cell types in large populations of diseased and healthy patients. It is thus necessary to understand the molecular mechanisms of disease-associated genetic variants and their potential effects in mediating microglial functions. To circumvent the differences between mouse and human microglia, novel methods have been recently developed to differentiate hPSCs, including hESCs and hiPSCs reprogrammed from patients’ somatic cells, as well as isogenic hPSCs edited with CRISPR/Cas9, into MGLs that can provide an unlimited source of human microglia, especially bearing those variants, for disease modeling and studying the mechanisms of microglial activation. CNS: Central nervous system; CRISPR: clustered regularly interspaced short palindromic repeats; ESCs: embryonic stem cells; GWAS: genome-wide association studies; hESCs: human embryonic stem cells; hPSCs: human pluripotent stem cells; iPSCs: induced pluripotent stem cells; MGLs: microglia-like cells; PBMCs: peripheral blood mononuclear cells; WES: whole exome sequencing; WGS: whole genome sequencing; WT: wild type.