Spatially mapped single-cell chromatin accessibility

Casey A. Thornton, Ryan M. Mulqueen, Kristof A. Torkenczy, Andrew Nishida, Eve G. Lowenstein, Andrew J. Fields, Frank J. Steemers, Wenri Zhang, Heather L. McConnell, Randy L. Woltjer, Anusha Mishra, Kevin M. Wright and Andrew C. Adey ()
Additional contact information
Casey A. Thornton: Oregon Health & Science University
Ryan M. Mulqueen: Oregon Health & Science University
Kristof A. Torkenczy: Oregon Health & Science University
Andrew Nishida: Oregon Health & Science University
Eve G. Lowenstein: Oregon Health & Science University
Andrew J. Fields: Oregon Health & Science University
Frank J. Steemers: Illumina Inc.
Wenri Zhang: Oregon Health & Science University
Heather L. McConnell: Oregon Health & Science University
Randy L. Woltjer: Oregon Health & Science University
Anusha Mishra: Oregon Health & Science University
Kevin M. Wright: Oregon Health & Science University
Andrew C. Adey: Oregon Health & Science University

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract High-throughput single-cell epigenomic assays can resolve cell type heterogeneity in complex tissues, however, spatial orientation is lost. Here, we present single-cell combinatorial indexing on Microbiopsies Assigned to Positions for the Assay for Transposase Accessible Chromatin, or sciMAP-ATAC, as a method for highly scalable, spatially resolved, single-cell profiling of chromatin states. sciMAP-ATAC produces data of equivalent quality to non-spatial sci-ATAC and retains the positional information of each cell within a 214 micron cubic region, with up to hundreds of tracked positions in a single experiment. We apply sciMAP-ATAC to assess cortical lamination in the adult mouse primary somatosensory cortex and in the human primary visual cortex, where we produce spatial trajectories and integrate our data with non-spatial single-nucleus RNA and other chromatin accessibility single-cell datasets. Finally, we characterize the spatially progressive nature of cerebral ischemic infarction in the mouse brain using a model of transient middle cerebral artery occlusion.

Date: 2021
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DOI: 10.1038/s41467-021-21515-7

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