Comparison of WT and CHD2 haploinsufficent human interneuron progenitor (hMGE) and interneuron (hcIN) models, to define differences in RNA expression, genomic accessibility and histone 3 lysine 27 acetylation

Background: Mutations in the chromatin remodeller CHD2 have been strongly associated with multiple neurodevelopmental disorders. However the precise function of CHD2 through neuronal development remains largely uncharacterized. Methods: We have used our protocol for generating cortical interneurons from human embryonic stem cells to study the role of CHD2 in cortical interneuron development, by comparing wild type hMGE and hcINs with a model with CHD2 haploinsufficency Results: This work found that CHD2 controls the expresson of genes with rolls in cell-cell interaction in neuronal precursors and directly influences the exprssion of genes necessary for the production of post-mitotic cortical interneurons Conclusions: As CHD2 plays distinct roles in several aspects of interneuron development, pathogenic CHD2 mutations have high potential to disrupt one or more of these events, contributing to neurodevelopmental disorders Overall design: For each time point, genotype and data set there are 2-4 biological replicates generated from parrellel differentiation from clonal hESC lines.