Integrated patient induced pluripotent stem cell models and Gaa-/- mice reveal central nervous system neural pathology in infantile-onset Pompe disease

Figure 2 Patient-specific induced pluripotent stem cell-derived neural cells exhibit cell-type-specific lysosomal pathology. A: Schematic diagram of the differentiation protocol to generate cortical neurons, astrocytes, oligodendrocytes, and spinal motor neurons; B-E: Representative immunofluorescence images and quantification of lysosomal size showing co-localization of the lysosomal marker LAMP2 (red) with lineage-specific markers (green): MBP (oligodendrocytes, B), GFAP (astrocytes, C), TUBB3 (cortical neurons, D), and ChAT (motor neurons, E). Nuclei were counterstained with DAPI (blue). Quantitative analysis revealed significant lysosomal enlargement in all infantile-onset Pompe disease-derived neural subtypes vs controls (oligodendrocytes: ^dP < 0.0001; astrocytes: ^dP < 0.0001; cortical neurons: ^cP < 0.001; motor neurons: ^cP < 0.001; unpaired two-tailed Student’s t-test). For each cell type, 10-15 cells were quantified per experiment from three independent differentiations. Data are presented as mean ± SEM. Scale bar = 50 μm. iPSCs: Induced pluripotent stem cell; IOPD: Infantile-onset Pompe disease.