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Citation
Bravo González-Blas, C., Quan, X.J., Duran-Romaña, R., Taskiran, I.I., Koldere, D., Davie, K., Christiaens, V., Makhzami, S., Hulselmans, G., de Waegeneer, M., Mauduit, D., Poovathingal, S., Aibar, S., Aerts, S. (2020). Identification of genomic enhancers through spatial integration of single-cell transcriptomics and epigenomics.  Mol. Syst. Biol. 16(5): e9438.
FlyBase ID
FBrf0245749
Publication Type
Research paper
Abstract

Single-cell technologies allow measuring chromatin accessibility and gene expression in each cell, but jointly utilizing both layers to map bona fide gene regulatory networks and enhancers remains challenging. Here, we generate independent single-cell RNA-seq and single-cell ATAC-seq atlases of the Drosophila eye-antennal disc and spatially integrate the data into a virtual latent space that mimics the organization of the 2D tissue using ScoMAP (Single-Cell Omics Mapping into spatial Axes using Pseudotime ordering). To validate spatially predicted enhancers, we use a large collection of enhancer-reporter lines and identify ~ 85% of enhancers in which chromatin accessibility and enhancer activity are coupled. Next, we infer enhancer-to-gene relationships in the virtual space, finding that genes are mostly regulated by multiple, often redundant, enhancers. Exploiting cell type-specific enhancers, we deconvolute cell type-specific effects of bulk-derived chromatin accessibility QTLs. Finally, we discover that Prospero drives neuronal differentiation through the binding of a GGG motif. In summary, we provide a comprehensive spatial characterization of gene regulation in a 2D tissue.

PubMed ID
PubMed Central ID
PMC7237818 (PMC) (EuropePMC)
Related Publication(s)
Note

Closing the gap: a roadmap to single-cell regulatory genomics.
Carnesecchi and Lohmann, 2020, Mol. Syst. Biol. 16(5): e9497 [FBrf0245819]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Syst. Biol.
    Title
    Molecular Systems Biology
    Publication Year
    2005-
    ISBN/ISSN
    1744-4292
    Data From Reference