Gene expression profile at single cell level of human control, MPHOSPH8-deficient and MORC2-deficient cerebral organoids at day 27.

To translate our mouse data and to model the role of MPHOSPH8 and MORC2 in human brain development, we generated human three-dimensional (3D) cerebral organoids lacking MPHOSPH8 and MORC2. These cerebral organoids were compared to control organoids by single cell RNA sequencing (scRNA-seq) to analyze the cell composition and expression of clustered protocadherins. Overall design: We established two independent clones of MPHOSPH8 as well as MORC2 knockout H9 human ES cell lines by CRISPR-Cas9 engineering and used these clones for cerebral organoid generation. On day 27 single-cell suspensions from two cerebral organoids per condition were prepared and analyzed by scRNA-seq.