Changes in H3K27me3 in Tatton-Brown-Rahman Syndrome Neuronal Progenitor Cells

Human pluripotent stem cell (hPSC) models of Tatton-Brown-Rahman Syndrome (TBRS) were generated (R882H and P904L), and compared to isogenically paired controls (C-WT and WT, respectively). These models were used to generate MGE-like ventral telencephalic neuronal progenitors (V-NPCs) and dorsally patterned neuronal progenitors modelling the cortical ventricular zone (D-NPCs). Cut and Tag for the tri-methylation of histone H3 at the lysine 27 residue (H3K27me3) was performed, to assess how loss of DNMT3A function due to TBRS-associated mutations affects deposition of H3K27me3 Overall design: For each cell type and cell line, 4 biological replicates were generated from independent differentiations of hPSCs and used to compare differences between each TBRS model and the paired isogenic control (R882H vs C-WT and P904L vs WT).