TY - JOUR
T1 - Spatially mapped single-cell chromatin accessibility
AU - Thornton, Casey A.
AU - Mulqueen, Ryan M.
AU - Torkenczy, Kristof A.
AU - Nishida, Andrew
AU - Lowenstein, Eve G.
AU - Fields, Andrew J.
AU - Steemers, Frank J.
AU - Zhang, Wenri
AU - McConnell, Heather L.
AU - Woltjer, Randy L.
AU - Mishra, Anusha
AU - Wright, Kevin M.
AU - Adey, Andrew C.
N1 - Funding Information:
We thank members of the Adey, O’Roak, and Wright labs for their support; Kylee Rosette for assistance with animal husbandry; Eleonora Juarez for discussion on protocol development; Anthony P. Barnes and Brian J. O’Roak for helpful discussions on experimental design; and Dominica Cao and Brooke DeRosa for IHC staining. This work was supported by the NIH Brain Initiative, National Institute for Drug Abuse (1R01DA047237), and the NIH National Institute for General Medical Studies (R35GM124704) to A.C.A.; and an OHSU Early Independence Fellowship to C.A.T.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85101584248&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101584248&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-21515-7
DO - 10.1038/s41467-021-21515-7
M3 - Article
C2 - 33627658
AN - SCOPUS:85101584248
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1274
ER -