02094nas a2200325   4500000000100000000000100001008004100002260001500043653001800058100001700076700001700093700002100110700001600131700001200147700001700159700002500176700001500201700001700216700001700233700001700250700002200267700001100289700002000300245013800320856005500458300000900513490000700522520122500529022001401754       2025                            d  c2025-08-0110aSchizophrenia1 aSneha B. Rao1 aZhixiong Sun1 aFrancesco Brundu1 aYannan Chen1 aYan Sun1 aHuixiang Zhu1 aRobert J. Shprintzen1 aRaju Tomer1 aRaul Rabadan1 aKam W. Leong1 aSander Markx1 aSteven A. Kushner1 aBin Xu1 aJoseph A. Gogos00aAberrant pace of cortical neuron development in brain organoids from patients with 22q11.2 deletion syndrome-associated schizophrenia  uhttps://www.nature.com/articles/s41467-025-62187-x  a69860 v163 aChildren 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. MicroRNA profiling suggests that DGCR8 haploinsufficiency contributes to these effects via dysregulation of genes that control the pace of maturation. Protein-protein interaction network analysis highlights complementary roles for additional deleted genes. Our study reveals consistent developmental and molecular defects caused by 22q11.2 deletions, offering insights into disease mechanisms and therapeutic strategies.  a2041-1723