Spatial profiling of chromatin accessibility in mouse and human tissues

Yanxiang Deng, Marek Bartosovic, Sai Ma, Di Zhang, Petra Kukanja, Yang Xiao, Graham Su, Yang Liu, Xiaoyu Qin, Gorazd B. Rosoklija, Andrew J. Dwork, J. John Mann, Mina L. Xu, Stephanie Halene, Joseph E. Craft, Kam W. Leong, Maura Boldrini, Gonçalo Castelo-Branco () and Rong Fan ()
Additional contact information
Yanxiang Deng: Yale University
Marek Bartosovic: Karolinska Institutet
Sai Ma: Broad Institute of MIT and Harvard
Di Zhang: Yale University
Petra Kukanja: Karolinska Institutet
Yang Xiao: Columbia University
Graham Su: Yale University
Yang Liu: Yale University
Xiaoyu Qin: Yale University
Gorazd B. Rosoklija: Columbia University
Andrew J. Dwork: Columbia University
J. John Mann: Columbia University
Mina L. Xu: Yale University School of Medicine
Stephanie Halene: Yale School of Medicine
Joseph E. Craft: Yale University School of Medicine
Kam W. Leong: Columbia University
Maura Boldrini: Columbia University
Gonçalo Castelo-Branco: Karolinska Institutet
Rong Fan: Yale University

Nature, 2022, vol. 609, issue 7926, 375-383

Abstract: Abstract Cellular function in tissue is dependent on the local environment, requiring new methods for spatial mapping of biomolecules and cells in the tissue context1. The emergence of spatial transcriptomics has enabled genome-scale gene expression mapping2–5, 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 chemistry6 and microfluidic deterministic barcoding5. 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.

Date: 2022
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DOI: 10.1038/s41586-022-05094-1

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