Abstract
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.
Original language | English |
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Pages (from-to) | 835-848 |
Number of pages | 14 |
Journal | Genome Research |
Volume | 30 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2020 Jun |
Bibliographical note
Funding Information:This work was supported by the National Institute of General Medical Sciences (R01-GM120033), National Science Foundation-Division of Mathematical Sciences (DMS-1263932), Cancer Prevention and Research Institute of Texas (RP170387), Houston Endowment, the Hamill Foundation, and Chao Family Foundation (Z.L.), Huffington Foundation, Howard Hughes Medical Institute (H.Y.Z.). L.W. was supported by a predoctoral fellowship from Autism Speaks (#9120).
Funding Information:
We thank Shu Zhang and Fuchou Tang for kindly sharing the detailed clustering result of cell subtypes, which can be downloaded now from the NCBI Gene Expression Omnibus (GEO; https://www .ncbi.nlm.nih.gov/geo/), accession number GSE104276. We thank Mingshan Xue, Dmitry Velmeshev, Hyun-Hwan Jeong, and Ying-Wooi Wan for valuable discussions. We thank V.L. Brandt for editing the manuscript. This work was supported by the National Institute of General Medical Sciences (R01-GM120033), National Science Foundation–Division of Mathematical Sciences (DMS-1263932), Cancer Prevention and Research Institute of Texas (RP170387), Houston Endowment, the Hamill Foundation, and Chao Family Foundation (Z.L.), Huf-fington Foundation, Howard Hughes Medical Institute (H.Y.Z.). L.W. was supported by a predoctoral fellowship from Autism Speaks (#9120).
Publisher Copyright:
© 2020 Cold Spring Harbor Laboratory Press. All rights reserved.
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)