Data from: Cell type-specific dysregulation of gene expression due to Chd8 haploinsufficiency during mouse cortical development

Disruptive variants in the chromodomain helicase CHD8, which acts as a
transcriptional regulator during neurodevelopment, are strongly associated
with risk for autism spectrum disorder (ASD). CHD8 haploinsufficiency is
hypothesized to contribute to ASD by perturbing neurodevelopmental gene
expression. However, insight into the cell-type-specific transcriptional
effects of CHD8 haploinsufficiency remains limited. We utilized
single-cell and single-nucleus RNA sequencing to globally profile gene
expression and identify dysregulated genes in the embryonic and juvenile
wild-type and Chd8+/− mouse cortex, respectively. Chd8 and other ASD
risk-associated genes showed a convergent expression trajectory that was
largely conserved between the mouse and human developing cortex,
increasing from the progenitor zones to the cortical plate. Genes
associated with risk for neurodevelopmental disorders and genes involved
in neuron projection development, chromatin remodeling, signaling, and
migration were dysregulated in Chd8+/− embryonic day (E) 12.5 radial glia.
Genes implicated in synaptic organization and activity were dysregulated
in Chd8+/− postnatal day (P) 25 deep- and upper-layer excitatory cortical
neurons, suggesting a delay in synaptic maturation or impaired
synaptogenesis. Our findings reveal a complex pattern of transcriptional
dysregulation in the Chd8+/− developing cortex, potentially with distinct
biological impacts on progenitors and maturing neurons in the excitatory
neuronal lineage.