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Spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissues at genome scale and cellular level

View ORCID ProfileYanxiang Deng, Marek Bartosovic, Sai Ma, Di Zhang, Yang Liu, Xiaoyu Qin, Graham Su, Mina L. Xu, View ORCID ProfileStephanie Halene, Joseph E. Craft, View ORCID ProfileGonçalo Castelo-Branco, View ORCID ProfileRong Fan
doi: https://doi.org/10.1101/2021.06.06.447244
Yanxiang Deng
1Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA
2Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA
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  • ORCID record for Yanxiang Deng
Marek Bartosovic
3Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
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Sai Ma
4Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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Di Zhang
1Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA
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Yang Liu
1Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA
2Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA
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Xiaoyu Qin
1Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA
2Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA
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Graham Su
1Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA
2Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA
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Mina L. Xu
5Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
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Stephanie Halene
2Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA
6Section of Hematology, Department of Internal Medicine, and Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA
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Joseph E. Craft
7Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
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Gonçalo Castelo-Branco
3Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
8Ming Wai Lau Centre for Reparative Medicine, Stockholm node, Karolinska Institutet, Stockholm, Sweden
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Rong Fan
1Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA
2Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA
9Human and Translational Immunology Program, Yale School of Medicine, New Haven, CT 06520, USA
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  • For correspondence: rong.fan@yale.edu
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Abstract

Cellular function in tissue is dependent upon the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context. The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping, but it remains elusive to capture spatial epigenetic information of tissue at cellular level and genome scale. Here we report on spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissue section via next-generation sequencing by combining in situ Tn5 transposition chemistry and microfluidic deterministic barcoding. Spatial chromatin accessibility profiling of mouse embryos delineated tissue region-specific epigenetic landscapes and identified gene regulators implicated in the central nerve system development. Mapping the accessible genome in human tonsil tissue with 20μm pixel size revealed spatially distinct organization of immune cell types and states in lymphoid follicles and extrafollicular zones. This technology takes spatial biology to a new realm by enabling spatially resolved epigenomics to improve our understanding of cell identity, state, and fate decision in relation to epigenetic underpinnings in development and disease.

Competing Interest Statement

R.F. and Y.D. are inventors of a patent application related to this work. R.F. is scientific founder and advisor of IsoPlexis, Singleron Biotechnologies, and AtlasXomics. The interests of R.F. were reviewed and managed by Yale University Provosts Office in accordance with the University conflict of interest policies.

Copyright 
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-ND 4.0 International license.
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Posted June 07, 2021.
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Spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissues at genome scale and cellular level
Yanxiang Deng, Marek Bartosovic, Sai Ma, Di Zhang, Yang Liu, Xiaoyu Qin, Graham Su, Mina L. Xu, Stephanie Halene, Joseph E. Craft, Gonçalo Castelo-Branco, Rong Fan
bioRxiv 2021.06.06.447244; doi: https://doi.org/10.1101/2021.06.06.447244
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Spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissues at genome scale and cellular level
Yanxiang Deng, Marek Bartosovic, Sai Ma, Di Zhang, Yang Liu, Xiaoyu Qin, Graham Su, Mina L. Xu, Stephanie Halene, Joseph E. Craft, Gonçalo Castelo-Branco, Rong Fan
bioRxiv 2021.06.06.447244; doi: https://doi.org/10.1101/2021.06.06.447244

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