Spatial chromatin architecture and accessibility co-profiling of mammalian tissues
Cellular function depends on the spatial organization of cells and biomolecules within the tissue microenvironment. Advances in spatial omics have enabled profiling of molecular features such as transcriptome, proteome and epigenome, and there has been rapid progress of imaging-based approaches to study spatial three-dimensional (3D) genome organization. Here we present Spatial-ATAC-Hi-C, a microfluidic‑based platform for genome-wide, spatially resolved joint-profiling of 3D genome organization and chromatin accessibility on tissue slides. Applied to mouse and human brains, Spatial-ATAC-Hi-C revealed distinct chromatin architecture and gene regulatory programs in neuronal and non-neuronal populations in their native tissue context. In glioblastoma and astrocytoma samples, we detected spatially resolved 3D genome alterations, copy number variations and structural variations across tumor regions, revealing clinically relevant oncogenic events and clonal heterogeneity. By co-profiling of genome architecture and chromatin accessibility while preserving tissue architecture, Spatial-ATAC-Hi-C provides a powerful tool for studying spatial gene regulation in human biology and disease.
Authors
- Hinda Najem (ORCID: https://orcid.org/0000-0003-4432-9708)
- Craig Horbinski (ORCID: https://orcid.org/0000-0001-8340-9992)
- Rong Fan (ORCID: https://orcid.org/0000-0001-7805-8059)
- Josiah Hiu-yuen Wong (ORCID: https://orcid.org/0009-0007-5176-2485)
- Yu Luan (ORCID: https://orcid.org/0000-0003-1778-9071)
- Yarui Diao (ORCID: https://orcid.org/0000-0001-5842-4082)
- Juan Wang (ORCID: https://orcid.org/0000-0003-0933-3744)
- Alok Swaroop (ORCID: https://orcid.org/0000-0003-0317-6688)
- Feng Yue (ORCID: https://orcid.org/0000-0002-7954-5462)
- Yihao Fu (ORCID: https://orcid.org/0000-0002-4605-0973)
- Amy B. Heimberger (ORCID: https://orcid.org/0000-0002-9970-8695)
- Di Zhang (ORCID: https://orcid.org/0000-0001-8466-9868)
- Bo Tao (ORCID: https://orcid.org/0000-0002-5490-4668)
- Shaojun Yu (ORCID: https://orcid.org/0000-0003-3938-5828)
- Cheng Yang
- Khizar R. Nandoliya
- Mark W. Youngblood
- Qixuan Wang
- Adam M. Sonabend
- Kathleen McCortney
- Ping Wang
Institutions
- Northwestern University (US)
- The University of Texas at San Antonio Health Science Center (US)
- Yale University (US)
- Duke Medical Center (US)
- Duke University Hospital (US)
- Neurological Surgery (US)
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Publication Details
- Journal
- Nature Methods
- Published
- 2026-09-01
- DOI
- https://doi.org/10.1038/s41592-026-03217-4
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Defense
- National Cancer Institute, Cairo University
- National Human Genome Research Institute
- National Institute of General Medical Sciences