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

Figure 1 Generation and validation of induced pluripotent stem cell line from an infantile-onset Pompe disease patient with central nervous system involvement. A: Cranial T2-weighted magnetic resonance imaging reveals bilateral frontoparietal white matter mild hyperintensity (orange arrows); B: Sanger sequencing confirms pathogenic variants in the acid α-glucosidase gene: C.1557G>A (p.M519I) and c.1798C>T (p.R600C); C: Immunofluorescence staining demonstrates expression of pluripotency markers (OCT4, SSEA4, NANOG, TRA1-60, and SOX2) in patient-derived induced pluripotent stem cells. Scale bar = 100 μm; D: G-banding shows a normal 46, XX karyotype in the established infantile-onset Pompe disease patient - specific induced pluripotent stem cell line; E: In vitro EB formation and immunofluorescence staining confirm trilineage differentiation potential, as evidenced by expression of hepatocyte nuclear factor 3-β (endoderm), α-smooth muscle actin (mesoderm), and Nestin (ectoderm). Scale bar = 100 μm. HNF3β: Hepatocyte nuclear factor 3-β; SMA: Smooth muscle actin.