Fig. 5

Characterization of the MDMi cell model. A Study design to assess functional effects of the TYROBP deletion in MDMi cells. B Decreased DAP12 protein levels in the monocytes and MDMi of monoallelic TYROBP deletion carriers compared to cells from individuals homozygous for the TYROBP common variant. DAP12 protein levels were normalized to GAPDH levels in the same lysate. Monocytes: T^CV, n = 4; T^del, n = 2; MDMi: T^CV, n = 2; T^del, n = 3. C TYROBP RNA levels are decreased in monocytes and MDMi of monoallelic TYROBP deletion carriers compared to cells from individuals homozygous for TYROBP common variant, while no TYROBP RNA is detected in NHD patients homozygous for the TYROBP deletion. Monocytes: T^CV, n = 2; T^del, n = 2; NHD, n = 2; MDMi: T^CV, n = 8; T^del, n = 3; NHD, n = 2. D Principal component analysis reveals that MDMi and iPSC-derived microglia (iMG) group closely together according to their expression profiles, which were different from their respective precursor cells, monocytes and iPSCs. E–F GSEA analysis shows that microglial genes are upregulated (E) while monocyte genes are downregulated (F) in the MDMi cells compared to monocytes. G TREM2 is not expressed in monocytes and is upregulated during MDMi differentiation in all genotype groups. Monocytes: T^CV, n = 2; T^del, n = 2; NHD, n = 2; MDMi: T^CV, n = 8; T^del, n = 3; NHD, n = 2. Data in B, C, and G are shown as mean ± SD. Each data point represents one individual