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The cis-regulatory dynamics of embryonic development at single cell resolution

View ORCID ProfileDarren A. Cusanovich, View ORCID ProfileJames P. Reddington, David A. Garfield, Riza Daza, Raquel Marco-Ferreres, Lena Christiansen, Xiaojie Qiu, Frank Steemers, View ORCID ProfileCole Trapnell, View ORCID ProfileJay Shendure, View ORCID ProfileEileen E.M. Furlong
doi: https://doi.org/10.1101/166066
Darren A. Cusanovich
1Department of Genome Sciences, University of Washington, Seattle, Washington, USA
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James P. Reddington
2European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany
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David A. Garfield
2European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany
3Current address: IRI Life Sciences, Humboldt Universität zu, Berlin
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Riza Daza
1Department of Genome Sciences, University of Washington, Seattle, Washington, USA
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Raquel Marco-Ferreres
2European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany
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Lena Christiansen
4Illumina, San Diego, California, USA
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Xiaojie Qiu
1Department of Genome Sciences, University of Washington, Seattle, Washington, USA
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Frank Steemers
4Illumina, San Diego, California, USA
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Cole Trapnell
1Department of Genome Sciences, University of Washington, Seattle, Washington, USA
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Jay Shendure
1Department of Genome Sciences, University of Washington, Seattle, Washington, USA
5Howard Hughes Medical Institute, Seattle, Washington, USA
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  • For correspondence: shendure@uw.edu furlong@embl.de
Eileen E.M. Furlong
2European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany
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  • For correspondence: shendure@uw.edu furlong@embl.de
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ABSTRACT

Single cell measurements of gene expression are providing new insights into lineage commitment, yet the regulatory changes underlying individual cell trajectories remain elusive. Here, we profiled chromatin accessibility in over 20,000 single nuclei across multiple stages of Drosophila embryogenesis. Our data reveal heterogeneity in the regulatory landscape prior to gastrulation that reflects anatomical position, a feature that aligns with future cell fate. During mid embryogenesis, tissue granularity emerges such that cell types can be inferred by their chromatin accessibility, while maintaining a signature of their germ layer of origin. We identify over 30,000 distal elements with tissue-specific accessibility. Using transgenic embryos, we tested the germ layer specificity of a subset of predicted enhancers, achieving near-perfect accuracy. Overall, these data demonstrate the power of shotgun single cell profiling of embryos to resolve dynamic changes in open chromatin during development, and to uncover the cis-regulatory programs of germ layers and cell types.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 20, 2017.
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The cis-regulatory dynamics of embryonic development at single cell resolution
Darren A. Cusanovich, James P. Reddington, David A. Garfield, Riza Daza, Raquel Marco-Ferreres, Lena Christiansen, Xiaojie Qiu, Frank Steemers, Cole Trapnell, Jay Shendure, Eileen E.M. Furlong
bioRxiv 166066; doi: https://doi.org/10.1101/166066
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The cis-regulatory dynamics of embryonic development at single cell resolution
Darren A. Cusanovich, James P. Reddington, David A. Garfield, Riza Daza, Raquel Marco-Ferreres, Lena Christiansen, Xiaojie Qiu, Frank Steemers, Cole Trapnell, Jay Shendure, Eileen E.M. Furlong
bioRxiv 166066; doi: https://doi.org/10.1101/166066

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