Identification of genomic enhancers through spatial integration of single‐cell transcriptomics and epigenomics
| Autor: | Suresh Poovathingal, Ibrahim Ihsan Taskiran, Xiao-Jiang Quan, Valerie Christiaens, Samira Makhzami, Duygu Koldere, Maxime de Waegeneer, Stein Aerts, Kristofer Davie, Ramon Duran-Romaña, Gert Hulselmans, Sara Aibar, Carmen Bravo González-Blas, David Mauduit |
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| Jazyk: | angličtina |
| Předmět: |
EXPRESSION
CHROMATIN Medicine (General) Biochemistry & Molecular Biology QH301-705.5 Gene regulatory network SHADOW ENHANCERS Computational biology GENE REGULATORY NETWORKS General Biochemistry Genetics and Molecular Biology ORGAN DEVELOPMENT 03 medical and health sciences PHOTORECEPTOR DIFFERENTIATION R5-920 0302 clinical medicine enhancer detection Gene expression PHENOTYPIC ROBUSTNESS single‐cell omics Biology (General) SINE-OCULIS Enhancer Gene 030304 developmental biology Epigenomics Regulation of gene expression 0303 health sciences Science & Technology General Immunology and Microbiology biology Applied Mathematics 030302 biochemistry & molecular biology Prospero biology.organism_classification eye-antennal disc spatial integration single-cell omics Chromatin DROSOPHILA EYE DEVELOPMENT R8 PHOTORECEPTOR Computational Theory and Mathematics eye‐antennal disc General Agricultural and Biological Sciences gene regulation Life Sciences & Biomedicine 030217 neurology & neurosurgery Information Systems |
| Zdroj: | Molecular Systems Biology Molecular Systems Biology, Vol 16, Iss 5, Pp n/a-n/a (2020) |
| ISSN: | 1744-4292 |
| DOI: | 10.15252/msb.20209438 |
| Popis: | 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. ispartof: MOLECULAR SYSTEMS BIOLOGY vol:16 issue:5 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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