Fig. 4

Patient-derived iMGs carrying GRN variants exhibit enlarged lysosomal abnormalities. A Fluorescence images of PGRN (red), Lysosome-associated membrane protein 1 (LAMP1, green), and IBA1 (purple) in control iMGs; DAPI-stained nuclei. Scale, 10 µm. B Images of LAMP1 and Transmembrane Protein 119 (TMEM119) in FTD–GRN and control iMGs; higher magnification of selected areas. DAPI nuclei. Scale, 10 µm. C LAMP1 intensity quantified in TMEM119⁺ iMGs, 50 + cells/subject, 5 experiments; mean ± SEM, **p < 0.01, ***p < 0.001 (one-way ANOVA with post hoc Tukey’s test). D LAMP1⁺ vesicle size quantification in iMGs, 50 + cells/subject, 3 experiments; mean ± SEM, ***p < 0.001, ****p < 0.0001 (one-way ANOVA with post hoc Tukey’s test). E mRNA of lysosome-related genes (LAMP1, LAMP2, CTSB, CTSD, ATP6AP2, and LGALS3) in FTD–GRN vs. control iMGs, normalized to control; mean ± SEM, *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001 (one-way ANOVA with post hoc Tukey’s test). F TFEB fluorescence in FTD–GRN and control iMGs; DAPI nuclei. Scale, 10 µm. G Nuclear TFEB cell count in iMGs (n = 50/subject); mean ± SEM, ****p < 0.0001 (one-way ANOVA with post hoc Tukey’s test). H Western blot for Sortilin1 (SORT1), TMEM106B, GAPDH in FTD–GRN and control iMGs; GAPDH as loading control