TY - JOUR
T1 - The accessible chromatin landscape of the murine hippocampus at single-cell resolution
AU - Sinnamon, John R.
AU - Torkenczy, Kristof A.
AU - Linhoff, Michael W.
AU - Vitak, Sarah A.
AU - Mulqueen, Ryan M.
AU - Pliner, Hannah A.
AU - Trapnell, Cole
AU - Steemers, Frank J.
AU - Mandel, Gail
AU - Adey, Andrew C.
N1 - Funding Information:
We thank Ryan Mulqueen and Andy Fields for helpful suggestions and contributions along with other members of the Adey Laboratory. This work was supported by NIH (NIGMS R35GM124704 and NIDA R01DA047237 to A.C.A., NS099374 to G.M., U54DK107979 and DP2HD088158 to C.T.), an NSF GRFP to H.A.P. (DGE-1256082), and support from the Rett Syndrome Research Trust to G.M.
Publisher Copyright:
© 2019 Sinnamon et al.
PY - 2019/5
Y1 - 2019/5
N2 - 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 a 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 data sets; and a valuable resource of hippocampal regulatory networks at single-cell resolution. We used sci-ATAC-seq to produce 2346 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. By using this data set, we identified eight distinct major clusters of cells representing both neuronal and nonneuronal cell types and characterized the driving regulatory factors and differentially accessible loci that define each cluster. Within pyramidal neurons, we identified four major clusters, including CA1 and CA3 neurons, and three additional subclusters. We then applied a recently described coaccessibility framework, Cicero, which identified 146,818 links between promoters and putative distal regulatory DNA. Identified coaccessibility networks showed cell-type specificity, shedding light on key dynamic loci that reconfigure to specify hippocampal cell lineages. Lastly, we performed 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 with nuclei from hippocampal tissue. This data set and accompanying analysis tools provide a new resource that can guide subsequent studies of the hippocampus.
AB - 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 a 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 data sets; and a valuable resource of hippocampal regulatory networks at single-cell resolution. We used sci-ATAC-seq to produce 2346 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. By using this data set, we identified eight distinct major clusters of cells representing both neuronal and nonneuronal cell types and characterized the driving regulatory factors and differentially accessible loci that define each cluster. Within pyramidal neurons, we identified four major clusters, including CA1 and CA3 neurons, and three additional subclusters. We then applied a recently described coaccessibility framework, Cicero, which identified 146,818 links between promoters and putative distal regulatory DNA. Identified coaccessibility networks showed cell-type specificity, shedding light on key dynamic loci that reconfigure to specify hippocampal cell lineages. Lastly, we performed 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 with nuclei from hippocampal tissue. This data set and accompanying analysis tools provide a new resource that can guide subsequent studies of the hippocampus.
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U2 - 10.1101/gr.243725.118
DO - 10.1101/gr.243725.118
M3 - Article
C2 - 30936163
AN - SCOPUS:85065511791
SN - 1088-9051
VL - 29
SP - 857
EP - 869
JO - PCR Methods and Applications
JF - PCR Methods and Applications
IS - 5
ER -