Cited by 417Single-cell and spatial transcriptomicsGenomics and Chromatin DynamicsEpigenetics and DNA Methylation

Spatial profiling of chromatin accessibility in mouse and human tissues

Open access
Deng, Yanxiang, Bartosovic, Marek, Ma, Sai, Zhang, Di, Kukanja, Petra, Xiao, Yang, Su, Graham, Liu, Yang +11 more·2022·Nature

Published version of a preprint

Abstract

Cellular function in tissue is dependent on the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context 1 . The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping 2–5 , but the ability to capture spatial epigenetic information of tissue at the cellular level and genome scale is lacking. Here we describe a method for spatially resolved chromatin accessibility profiling of tissue sections using next-generation sequencing (spatial-ATAC-seq) by combining in situ Tn5 transposition chemistry 6 and microfluidic deterministic barcoding 5 . Profiling mouse embryos using spatial-ATAC-seq delineated tissue-region-specific epigenetic landscapes and identified gene regulators involved in the development of the central nervous system. Mapping the accessible genome in the mouse and human brain revealed the intricate arealization of brain regions. Applying spatial-ATAC-seq to tonsil tissue resolved the spatially distinct organization of immune cell types and states in lymphoid follicles and extrafollicular zones. This technology progresses spatial biology by enabling spatially resolved chromatin accessibility profiling to improve our understanding of cell identity, cell state and cell fate decision in relation to epigenetic underpinnings in development and disease.

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Authors
Deng, Y., Bartosovic, M., Ma, S., Zhang, D., Kukanja, P., Xiao, Y., Su, G., Liu, Y., Qin, X., Rosoklija, G. B., Dwork, A. J., Mann, J. J., Xu, M. L., Halene, S., Craft, J. E., Leong, K. W., Boldrini, M., Castelo-Branco, G., & Fan, R.
Affiliations
  • Yale Cancer Center (US)
  • Broad Institute (US)
  • Yale University (US)
  • Karolinska Institutet (SE)
  • Columbia University (US)
  • Macedonian Academy of Sciences and Arts (MK)
  • New York State Psychiatric Institute (US)
  • Columbia University Irving Medical Center (US)
Corresponding author
Fan, Rong
Venue
Nature
Published
2022-08-17
Volume
609
Issue
7926
Pages
375-383
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W4292121951
Cited by
417
References
75
Citations by year
2026: 105 · 2025: 106 · 2024: 84 · 2023: 91 · 2022: 25 · 2021: 5
FWCI
24.97
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • ImmPort
Funders
  • Yale University
  • Li Ka Shing Foundation
  • Society for Immunotherapy of Cancer
  • Göran Gustafssons Stiftelser
  • European Commission (681893, HORIZON2020)
  • Cancerfonden (190394 Pj, 2019-)
  • Svenska Sällskapet för Medicinsk Forskning (JUB2019)
  • Karolinska Institutet
  • Knut och Alice Wallenbergs Stiftelse (2019–0107)
  • Vetenskapsrådet (2019-01360)
  • National Institutes of Health (UH3TR002151, 1rf1mh128876-01, UL1TR001863)
  • Stand Up To Cancer
  • National Institute on Aging (U54AG076043)
  • National Institute of Mental Health (RF1 MH128876)
  • National Cancer Institute (UH3CA257393, UG3CA257393, U54CA209992, R01CA245313, U01CA260507)
  • National Institute of Diabetes and Digestive and Kidney Diseases (U54DK106857)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R37AR040072)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
spatial epigenomics, mouse embryo development, central nervous system development, brain regionalization, tonsil, lymphoid follicles
MeSH terms
Chromatin Immunoprecipitation Sequencing, Animals, Brain, Cell Differentiation, Chromatin, Humans, Palatine Tonsil, Genome, Cell Lineage, Gene Expression Profiling, Chromatin Assembly and Disassembly, Mice, Epigenomics, High-Throughput Nucleotide Sequencing

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