biostudies-literaturePang KHuffington Foundationthe Hamill FoundationHoward Hughes Medical InstituteAutism SpeaksDivision of Mathematical SciencesHouston EndowmentNational Institute of General Medical SciencesNIGMS NIH HHSChao Family FoundationCancer Prevention and Research Institute of TexasNational Science Foundation835-848https://www.ebi.ac.uk/biostudies/studies/S-EPMC7370880biostudies-literatureUnknown30(6)A large number of genes have been implicated in neurodevelopmental disorders (NDDs), but their contributions to NDD pathology are difficult to decipher without understanding their diverse roles in different brain cell types. Here, we integrated NDD genetics with single-cell RNA sequencing data to assess coexpression enrichment patterns of various NDD gene sets. We identified midfetal cortical neural progenitor cell development-more specifically, the ventricular radial glia-to-intermediate progenitor cell transition at gestational week 10-as a key point of convergence in autism spectrum disorder (ASD) and epilepsy. Integrated Gene Ontology-based analysis further revealed that ASD genes activate neural differentiation and inhibit cell cycle during the transition, whereas epilepsy genes function as downstream effectors in the same processes, offering one possible explanation for the high comorbidity rate of the two disorders. This approach provides a framework for investigating the cell-type-specific pathophysiology of NDDs.Genome researchCoexpression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders.PMC7370880DMS-1263932R01-GM120033R01 GM120033RP1703879120Cheng CLiu ZHan KZoghbi HYWang WPang KWang LZhou JfalseCoexpression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders.A large number of genes have been implicated in neurodevelopmental disorders (NDDs), but their contributions to NDD pathology are difficult to decipher without understanding their diverse roles in different brain cell types. Here, we integrated NDD genetics with single-cell RNA sequencing data to assess coexpression enrichment patterns of various NDD gene sets. We identified midfetal cortical neural progenitor cell development-more specifically, the ventricular radial glia-to-intermediate progenitor cell transition at gestational week 10-as a key point of convergence in autism spectrum disorder (ASD) and epilepsy. Integrated Gene Ontology-based analysis further revealed that ASD genes activate neural differentiation and inhibit cell cycle during the transition, whereas epilepsy genes function as downstream effectors in the same processes, offering one possible explanation for the high comorbidity rate of the two disorders. This approach provides a framework for investigating the cell-type-specific pathophysiology of NDDs.2020-01-01T00:00:00Z2020 Jun2026-05-08T16:17:15.373Z2021-02-20T02:50:26ZS-EPMC73708803255477910.1101/gr.254987.119