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The accessible chromatin landscape of the hippocampus at single-cell resolution

View ORCID ProfileJohn R. Sinnamon, Kristof A. Torkenczy, Michael W. Linhoff, Sarah Vitak, View ORCID ProfileHannah A. Pliner, View ORCID ProfileCole Trapnell, Frank J. Steemers, View ORCID ProfileGail Mandel, View ORCID ProfileAndrew C. Adey
doi: https://doi.org/10.1101/407668
John R. Sinnamon
1The Vollum Institute, Oregon Health & Science University, Portland, OR, USA
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  • For correspondence: adey@ohsu.edu sinnamon@ohsu.edu
Kristof A. Torkenczy
2Oregon Health & Science University, Department of Molecular and Medical Genetics, Portland, OR, USA
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Michael W. Linhoff
1The Vollum Institute, Oregon Health & Science University, Portland, OR, USA
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Sarah Vitak
2Oregon Health & Science University, Department of Molecular and Medical Genetics, Portland, OR, USA
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Hannah A. Pliner
3University of Washington, Department of Genome Sciences, Seattle, WA, USA
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Cole Trapnell
3University of Washington, Department of Genome Sciences, Seattle, WA, USA
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Frank J. Steemers
4Illumina, Inc., San Diego, CA, USA
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Gail Mandel
1The Vollum Institute, Oregon Health & Science University, Portland, OR, USA
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Andrew C. Adey
2Oregon Health & Science University, Department of Molecular and Medical Genetics, Portland, OR, USA
5Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA
6Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
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  • For correspondence: adey@ohsu.edu sinnamon@ohsu.edu
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ABSTRACT

Here we present a comprehensive map of the accessible chromatin landscape of the mouse hippocampus at single-cell resolution. Substantial advances of this work include the optimization of single-cell combinatorial indexing assay for transposase accessible chromatin (sci-ATAC-seq), a software suite, scitools, for the rapid processing and visualization of single-cell combinatorial indexing datasets, and a valuable resource of hippocampal regulatory networks at single-cell resolution. We utilized sci-ATAC-seq to produce 2,346 high-quality single-cell chromatin accessibility maps with a mean unique read count per cell of 29,201 from both fresh and frozen hippocampi, observing little difference in accessibility patterns between the preparations. Using this dataset, we identified eight distinct major clusters of cells representing both neuronal and non-neuronal cell types and characterized the driving regulatory factors and differentially accessible loci that define each cluster. We then applied a recently described co-accessibility framework, Cicero, which identified 146,818 links between promoters and putative distal regulatory DNA. Identified co-accessibility networks showed cell-type specificity, shedding light on key dynamic loci that reconfigure to specify hippocampal cell lineages. Lastly, we carried out an additional sci-ATAC-seq preparation from cultured hippocampal neurons (899 high-quality cells, 43,532 mean unique reads) that revealed substantial alterations in their epigenetic landscape compared to nuclei from hippocampal tissue. This dataset and accompanying analysis tools provide a new resource that can guide subsequent studies of the hippocampus.

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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 September 04, 2018.
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The accessible chromatin landscape of the hippocampus at single-cell resolution
John R. Sinnamon, Kristof A. Torkenczy, Michael W. Linhoff, Sarah Vitak, Hannah A. Pliner, Cole Trapnell, Frank J. Steemers, Gail Mandel, Andrew C. Adey
bioRxiv 407668; doi: https://doi.org/10.1101/407668
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The accessible chromatin landscape of the hippocampus at single-cell resolution
John R. Sinnamon, Kristof A. Torkenczy, Michael W. Linhoff, Sarah Vitak, Hannah A. Pliner, Cole Trapnell, Frank J. Steemers, Gail Mandel, Andrew C. Adey
bioRxiv 407668; doi: https://doi.org/10.1101/407668

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