Aberrant pace of cortical neuron development in brain organoids from patients with 22q11.2 deletion syndrome and schizophrenia. [scRNA-Seq]

Adults and children with the 22q11.2 deletion syndrome (22q11.2DS) demonstrate cognitive, social and emotional impairments and markedly increased risk for schizophrenia (SCZ). The alterations in early human brain development resulting from this deletion remain unclear. Here we use organoid models of the developing human cerebral cortex derived from patients with 22q11.2DS and SCZ as well as unaffected controls to identify cell-type-specific developmental abnormalities that result from this genomic lesion. Using RNA-sequencing and follow-up experimental validation we find that loss of genes within the 22q11.2 locus leads to delayed development of cortical neurons.