Single cell profiling of the cerebral organoids derived from Schinzel-Giedion syndrome cells and isogenic controls

Schinzel-Giedion syndrome (SGS) is a developmental syndrome, due to SETBP1 gene mutations inducing the accumulation of the relative protein, which is fatal in early infancy. Here, we generated unpatterned cerebral organoids from both SGS iPSC line and isogenic control line (through CRISPR/Cas9 back correction). We showed that SEBP1 accumulation triggers the development of large and convoluted epithelial folds in SGS cerebral organoids. To thoroughly characterize the 3D organoids we used scRNAseq (10X platform) in which we evidences the presence of both neural progenitors and committed neural progenitors with aberrant gene signature in SGS organoids that possibly sustain the lateral increase of the neuroepithelium 1 organoid SEBP1 D686D (WT) and 1 organoid SEBP1 D686N (Mut)