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.

中文翻译：

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在单细胞水平上的共表达富集分析揭示了神经祖细胞中的收敛缺陷及其在神经发育障碍中的细胞类型转变。

大量基因已经牵涉到神经发育障碍（NDD），但是如果不了解它们在不同脑细胞类型中的不同作用，就很难解读它们对NDD病理学的贡献。在这里，我们将NDD遗传学与单细胞RNA测序数据整合在一起，以评估各种NDD基因集的共表达富集模式。我们确定了胎儿中枢皮质神经祖细胞的发育-更具体地说，在妊娠第10周时从心室放射状胶质细胞过渡到中间祖细胞-是自闭症谱系障碍（ASD）和癫痫症收敛的关键点。基于整合基因本体论的分析进一步揭示，ASD基因在过渡过程中激活神经分化并抑制细胞周期，而癫痫基因在相同过程中充当下游效应器，为这两种疾病的高合并症率提供了一种可能的解释。该方法提供了研究NDD的细胞类型特异性病理生理学的框架。