RT Journal
A1 Pang, Kaifang
A1 Wang, Li
A1 Wang, Wei
A1 Zhou, Jian
A1 Cheng, Chao
A1 Han, Kihoon
A1 Zoghbi, Huda Y.
A1 Liu, Zhandong
T1 Coexpression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders
JF Genome Research 
JO Genome Research 
YR 2020 
FD June 01 
VO 30 
IS 6 
SP 835 
OP 848 
DO 10.1101/gr.254987.119 
UL http://genome.cshlp.org/content/30/6/835.abstract 
AB 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.