hiPSC lines were generated from apoE3/3 and apoE4/4 subjects (Supplementary Table 1) as described16,17. All hiPSC lines were morphologically similar to embryonic stem (ES) cells (Supplementary Fig. 1b) and expressed ES cell markers, such as Nanog, Sox2, TRA-1-60, and TRA-1-81 (Supplementary Fig. 1c–e). DNA sequencing confirmed the apoE genotypes of all hiPSC lines, and chromosomal analysis revealed normal karyotypes (Supplementary Fig. 1f). After injection into immunodeficient mice, all hiPSC lines formed teratomas, confirming their pluripotency16,17. Three apoE3/3-hiPSC lines (E3/3-A, E3/3-B, and E3/3-C) and three apoE4/4-hiPSC lines (E4/4-A, E4/4-B, E4/4-C), each derived from a subject with the corresponding apoE genotype, were fully characterized and used in the current study (Supplementary Table 1). All six of these hiPSC lines developed well into neural stem cells expressing Sox2, nestin, Pax6, and FoxG1 (Supplementary Fig. 1g–i) and then into mature neurons that had neuronal morphology (Supplementary Fig. 1j) and expressed neuronal markers, Tuj1 and MAP2 (Supplementary Fig. 1k,l). Quantification shows that 90 ± 1.5% (mean ± SEM, n = 12 randomly collected images from three independent experiments with total of 326 cells counted) of the cells are positive for neuronal marker, MAP2, indicating the high purity of neuronal culture.
