PMID- 35978191 OWN - NLM STAT- MEDLINE VI - 609 IP - 7926 TI - Spatial profiling of chromatin accessibility in mouse and human tissues. PG - 375-383 CI - © 2022. The Author(s). LA - eng PT - Journal Article PL - England TA - Nature JT - Nature JID - 0410462 IS - 1476-4687 (Electronic) LID - 10.1038/s41586-022-05094-1 [doi] FAU - Deng, Yanxiang AU - Deng Y AUID- ORCID: http://orcid.org/0000-0002-9975-8086 AD - Department of Biomedical Engineering, Yale University, New Haven, CT, USA. AD - Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. FAU - Bartosovic, Marek AU - Bartosovic M AD - Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. FAU - Ma, Sai AU - Ma S AUID- ORCID: http://orcid.org/0000-0002-9785-7929 AD - Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. FAU - Zhang, Di AU - Zhang D AUID- ORCID: http://orcid.org/0000-0001-8466-9868 AD - Department of Biomedical Engineering, Yale University, New Haven, CT, USA. FAU - Kukanja, Petra AU - Kukanja P AUID- ORCID: http://orcid.org/0000-0003-1228-5923 AD - Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. FAU - Xiao, Yang AU - Xiao Y AUID- ORCID: http://orcid.org/0000-0001-7878-4923 AD - Department of Biomedical Engineering, Columbia University, New York, NY, USA. FAU - Su, Graham AU - Su G AD - Department of Biomedical Engineering, Yale University, New Haven, CT, USA. AD - Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. FAU - Liu, Yang AU - Liu Y AD - Department of Biomedical Engineering, Yale University, New Haven, CT, USA. AD - Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. FAU - Qin, Xiaoyu AU - Qin X AD - Department of Biomedical Engineering, Yale University, New Haven, CT, USA. AD - Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. FAU - Rosoklija, Gorazd B AU - Rosoklija GB AD - Department of Psychiatry, Columbia University, New York, NY, USA. AD - Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA. AD - Macedonian Academy of Sciences & Arts, Skopje, Republic of Macedonia. FAU - Dwork, Andrew J AU - Dwork AJ AD - Department of Psychiatry, Columbia University, New York, NY, USA. AD - Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA. AD - Macedonian Academy of Sciences & Arts, Skopje, Republic of Macedonia. AD - Department of Pathology and Cell Biology, Columbia University, New York, NY, USA. FAU - Mann, J John AU - Mann JJ AUID- ORCID: http://orcid.org/0000-0002-0265-6586 AD - Department of Psychiatry, Columbia University, New York, NY, USA. AD - Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA. AD - Department of Radiology, Columbia University, New York, NY, USA. FAU - Xu, Mina L AU - Xu ML AUID- ORCID: http://orcid.org/0000-0001-9513-245X AD - Department of Pathology, Yale University School of Medicine, New Haven, CT, USA. FAU - Halene, Stephanie AU - Halene S AUID- ORCID: http://orcid.org/0000-0002-2737-9810 AD - Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. AD - Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. AD - Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, CT, USA. FAU - Craft, Joseph E AU - Craft JE AUID- ORCID: http://orcid.org/0000-0002-1368-6756 AD - Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. FAU - Leong, Kam W AU - Leong KW AD - Department of Biomedical Engineering, Columbia University, New York, NY, USA. AD - Department of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA. FAU - Boldrini, Maura AU - Boldrini M AUID- ORCID: http://orcid.org/0000-0003-3574-7641 AD - Department of Psychiatry, Columbia University, New York, NY, USA. AD - Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA. FAU - Castelo-Branco, Gonçalo AU - Castelo-Branco G AUID- ORCID: http://orcid.org/0000-0003-2247-9393 AD - Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. goncalo.castelo-branco@ki.se. AD - Ming Wai Lau Centre for Reparative Medicine, Stockholm node, Karolinska Institutet, Stockholm, Sweden. goncalo.castelo-branco@ki.se. FAU - Fan, Rong AU - Fan R AUID- ORCID: http://orcid.org/0000-0001-7805-8059 AD - Department of Biomedical Engineering, Yale University, New Haven, CT, USA. rong.fan@yale.edu. AD - Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. rong.fan@yale.edu. AD - Department of Pathology, Yale University School of Medicine, New Haven, CT, USA. rong.fan@yale.edu. AD - Human and Translational Immunology Program, Yale School of Medicine, New Haven, CT, USA. rong.fan@yale.edu. IS - 0028-0836 (Linking) RN - 0 (Chromatin) SB - IM MH - Animals MH - Brain/metabolism MH - Cell Differentiation MH - Cell Lineage MH - *Chromatin/genetics/metabolism MH - *Chromatin Assembly and Disassembly/genetics MH - *Chromatin Immunoprecipitation Sequencing/methods MH - Epigenomics MH - Gene Expression Profiling MH - Genome MH - High-Throughput Nucleotide Sequencing/methods MH - Humans MH - Mice MH - Palatine Tonsil/cytology/immunology PMC - PMC9452302 DCOM- 20220909 LR - 20230724 DP - 202209 DEP - 20220817 AB - 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.