NGLY1-deficient cerebral organiods display abnormal neuronal differentiation

We report using a single-cell transcriptomic study of cerebral organiods (COs) developed from WA09 hESCs with gene editing-induced NGLY1 mutations and from NGLY1-deficient patient's hiPSCs at 40 or 80 days of development. WA09 hESC-derived COs with and without mutant NGLY1 and patient's hiPSC-derived COs with and without the ectopic expression NGLY1 were analyzed. The COs of two hESC clones with (NGLY1-deficient or NGLY1-functional) were cultured for 80 days of developments. Replicate deficient and functional CO samples were taken at 80 days and an additional sample was taken at day 40. The COs of two hiPSC clones (one NGLY1-deficient, one NGLY1-functional due to ectopic expression) were also cultured and sampled at 40 days of development.