MECP2-related pathways are dysregulated in a cortical organoid model of Myotonic dystrophy [scRNA-Seq]

As cortical organoids consist of a heterogeneous population of cell-types, 6-month-old DM1 and Rett syndrome cortical organoids were subjected to single cell RNA-seq (scRNA-seq) analysis to determine which cell type(s) CELF2’s RNA targets are expressed in. Unsupervised clustering was implemented on the combined dataset of 8595 cells from control, DM600, and DM1200 cortical organoids that consisted of ~2865 cells per organoid line and ~17,575 reads per cell to identify genotype-specific clusters at 6-months post-differentiation. Uniform Manifold Approximation and Projection (UMAP) for dimension reduction revealed clear differences between control and DM1 organoids. From the expression of established cell-type specific gene markers, smaller sub-clusters were combined to represent four major cell classes: neural progenitors, intermediate neural progenitors, glutamatergic cortical neurons, and glial cells. Gene expression profile at single cell level of cortical organoids differentiated from myotonic dystrophy 1(DM1200 and Dm600) and Rett Syndrome (MECP2) patient stem cells as well as 2 neurotypical control stem cells (MECP2_KO and MECP2_WT)