The generation of hCS from hPSC was performed as previously described11. To initiate the generation of hCS or hSS, intact hiPSC colonies were lifted from the plates using dispase (0.35 mg/ml) and transferred into ultralow attachment plastic dishes (Corning) in hPSC medium supplemented with the two SMAD inhibitors dorsomorphin (DM; 5 μM; Sigma) and SB-431542 (SB; 10 μM, Tocris), and the ROCK inhibitor Y-27632 (10 μM; EMD Chemicals). For the first five days, the hPSC medium was changed every day and supplemented with dorsomorphin and SB-431542. On the sixth day in suspension, neural spheroids were transferred to neural medium (NM) containing Neurobasal-A (Life Technologies, 10888), B-27 supplement without vitamin A (Life Technologies, 12587), GlutaMax (Life Technologies, 1:100), penicillin and streptomycin (Life Technologies, 1:100) and supplemented with the growth factors EGF (20 ng/ml; R&D Systems) and FGF2 (20 ng/ml; R&D Systems) until day 24. For the generation of hSS, the medium was supplemented with additional small molecules during the first 23 days in culture; a schematic showing the recipes is presented in Supplementary Fig. 4a). The hSS-IS condition involved the addition
