Identification of genomic enhancers through spatial integration of single‐cell transcriptomics and epigenomics
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 atlase...
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doaj-32070ef12bcb4df19d0631375f7ed3e52021-08-02T12:00:58ZengWileyMolecular Systems Biology1744-42922020-05-01165n/an/a10.15252/msb.20209438Identification of genomic enhancers through spatial integration of single‐cell transcriptomics and epigenomicsCarmen Bravo González‐Blas0Xiao‐Jiang Quan1Ramon Duran‐Romaña2Ibrahim Ihsan Taskiran3Duygu Koldere4Kristofer Davie5Valerie Christiaens6Samira Makhzami7Gert Hulselmans8Maxime deWaegeneer9David Mauduit10Suresh Poovathingal11Sara Aibar12Stein Aerts13VIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumVIB Center for Brain & Disease Research Leuven BelgiumAbstract 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.https://doi.org/10.15252/msb.20209438enhancer detectioneye‐antennal discgene regulationsingle‐cell omicsspatial integration |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Carmen Bravo González‐Blas Xiao‐Jiang Quan Ramon Duran‐Romaña Ibrahim Ihsan Taskiran Duygu Koldere Kristofer Davie Valerie Christiaens Samira Makhzami Gert Hulselmans Maxime deWaegeneer David Mauduit Suresh Poovathingal Sara Aibar Stein Aerts |
spellingShingle |
Carmen Bravo González‐Blas Xiao‐Jiang Quan Ramon Duran‐Romaña Ibrahim Ihsan Taskiran Duygu Koldere Kristofer Davie Valerie Christiaens Samira Makhzami Gert Hulselmans Maxime deWaegeneer David Mauduit Suresh Poovathingal Sara Aibar Stein Aerts Identification of genomic enhancers through spatial integration of single‐cell transcriptomics and epigenomics Molecular Systems Biology enhancer detection eye‐antennal disc gene regulation single‐cell omics spatial integration |
author_facet |
Carmen Bravo González‐Blas Xiao‐Jiang Quan Ramon Duran‐Romaña Ibrahim Ihsan Taskiran Duygu Koldere Kristofer Davie Valerie Christiaens Samira Makhzami Gert Hulselmans Maxime deWaegeneer David Mauduit Suresh Poovathingal Sara Aibar Stein Aerts |
author_sort |
Carmen Bravo González‐Blas |
title |
Identification of genomic enhancers through spatial integration of single‐cell transcriptomics and epigenomics |
title_short |
Identification of genomic enhancers through spatial integration of single‐cell transcriptomics and epigenomics |
title_full |
Identification of genomic enhancers through spatial integration of single‐cell transcriptomics and epigenomics |
title_fullStr |
Identification of genomic enhancers through spatial integration of single‐cell transcriptomics and epigenomics |
title_full_unstemmed |
Identification of genomic enhancers through spatial integration of single‐cell transcriptomics and epigenomics |
title_sort |
identification of genomic enhancers through spatial integration of single‐cell transcriptomics and epigenomics |
publisher |
Wiley |
series |
Molecular Systems Biology |
issn |
1744-4292 |
publishDate |
2020-05-01 |
description |
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. |
topic |
enhancer detection eye‐antennal disc gene regulation single‐cell omics spatial integration |
url |
https://doi.org/10.15252/msb.20209438 |
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