Coexpression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders

• DOI: 10.1101/gr.254987.119
• Publication Date: 2020-06-19T00:47:16Z
• Authors: Kaifang Pang; Li Wang; Wei Wang; Jian Zhou; Chao Cheng; Kihoon Han; Huda Y. Zoghbi; Zhandong Liu
• Keywords: Cell type; Progenitor

A large number of genes have been implicated in neurodevelopmental disorders (NDDs), but their contributions to NDD pathology are difficult decipher without understanding diverse roles different brain cell types. Here, we integrated genetics with single-cell RNA sequencing data assess coexpression enrichment patterns various gene sets. We identified midfetal cortical neural progenitor development—more specifically, the ventricular radial glia-to-intermediate transition at gestational week 10—as a key point convergence autism spectrum disorder (ASD) and epilepsy. Integrated Gene Ontology–based analysis further revealed that ASD activate differentiation inhibit cycle during transition, whereas epilepsy function as downstream effectors same processes, offering one possible explanation for high comorbidity rate two disorders. This approach provides framework investigating cell-type-specific pathophysiology NDDs.