Co-expression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders
Recent large-scale sequencing studies have identified a great number of genes whose disruptions cause neurodevelopmental disorders (NDDs). However, cell-type-specific functions of NDD genes and their contributions to NDD pathology are unclear. Here, we integrated NDD genetics with single-cell RNA sequencing data to identify cell-type and temporal convergence of genes involved in different NDDs. By assessing the co-expression enrichment pattern of various NDD gene sets, we identified mid-fetal cortical neural progenitor cell development--more specifically, ventricular radial glia-to-intermediate progenitor cell transition at gestational week 10--as a key convergent point in autism spectrum disorder (ASD) and epilepsy. Integrated gene ontology-based analyses further revealed that ASD genes function as upstream regulators to activate neural differentiation and inhibit cell cycle during the transition, whereas epilepsy genes function as downstream effectors in the same processes, offering a potential explanation for the high comorbidity rate of the two disorders. Together, our study provides a framework for investigating the cell-type-specific pathophysiology of NDDs.
- Downloaded 874 times
- Download rankings, all-time:
- Site-wide: 29,974
- In genetics: 1,367
- Year to date:
- Site-wide: 134,193
- Since beginning of last month:
- Site-wide: 103,444
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!