Coexpression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders.
Kaifang PangLi WangWei WangJian ZhouChao ChengKihoon HanHuda Y ZoghbiZhandong LiuPublished in: Genome research (2020)
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.
Keyphrases
- single cell
- autism spectrum disorder
- genome wide
- cell cycle
- rna seq
- genome wide identification
- attention deficit hyperactivity disorder
- high throughput
- genome wide analysis
- cell proliferation
- intellectual disability
- heart failure
- dna methylation
- stem cells
- pregnant women
- network analysis
- copy number
- electronic health record
- gene expression
- left ventricular
- white matter
- body mass index
- big data
- physical activity
- cell therapy
- ultrasound guided
- bone marrow
- data analysis
- atrial fibrillation
- placebo controlled