Aberrant pace of cortical neuron development in brain organoids from patients with 22q11.2 deletion syndrome-associated schizophrenia.

ABSTRACT: Children and adults with 22q11.2 deletion syndrome (22q11.2DS) experience cognitive and emotional challenges and face a markedly increased risk for schizophrenia (SCZ), yet how this deletion alters early human brain development remains unclear. Using cerebral cortex organoids derived from individuals with 22q11.2DS and SCZ, we identify cell-type-specific developmental abnormalities. Single-cell RNA sequencing and experimental validation reveal delayed cortical neuron maturation, with increased neural progenitor proliferation and a reduced proportion of more mature neurons. We observe disrupted molecular programs linked to neuronal maturation, sparser neurites, and blunted glutamate-induced Ca²⁺ responses. The aberrant transcriptional profile is enriched for neuropsychiatric risk genes. Mic

SUBMITTER: Rao SB 

PROVIDER: S-EPMC12316906 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature