Spatial epigenomics

01Overview and value chain#

Markers EC: In Vitro Diagnostic Regulation (IVDR) Class C | OECD: Genomics & bioinformatics | Regulator: FDA (US), EMA (EU), NMPA (China)

Spatial epigenomics maps the epigenetic landscape — chromatin accessibility, DNA methylation and histone modifications — while preserving the spatial architecture of the tissue under study. Traditional bulk or even single-cell ATAC-seq requires fully dissociating tissue into individual cells, a step that destroys information about cell-to-cell positioning, oxygen gradients and spatial interactions. Preserving a spatial map of histone methylation marks (H3K4me3 marking active promoters, H3K27me3 marking silenced regions) reveals how cells shift phenotype under the influence of neighboring cells or therapeutic drugs — directly relevant to studying tumor cell subpopulations and their microenvironment. Following Bruker’s 2024 acquisition of NanoString’s spatial biology business, the CosMx platform now images the whole transcriptome at single-cell resolution via a 6,000-plex RNA assay, while Vizgen’s newly launched MERFISH 2.0 chemistry and enhanced OmniVue panels extend spatial multi-omics with ADC biomarker capability. Innovative spatial barcoding methods — Spatial ATAC-seq, Spatial CUT&Tag, and multiplexed fluorescent in situ hybridization (FISH) — are the technical core of the field.

The key directions of spatial epigenomics are:

1. Deterministic tissue barcoding in microchannels (DBiT-seq): flowing unique oligonucleotide barcodes through mutually perpendicular microchannels laid over a tissue section, creating a 2D coordinate grid (X, Y) at resolution down to 10 microns.
2. Spatial Tn5 transposition: using modified Tn5 transposase to simultaneously fragment open chromatin and ligate adapters directly inside cell nuclei on a tissue section.
3. Spatial CUT&Tag and CUT&RUN: antibody-guided, in situ tethering of Tn5 or micrococcal nuclease to specific histone marks, mapping their genome-wide distribution while preserving tissue coordinates.
4. 3D epigenetic atlas reconstruction: bioinformatic integration of coordinate-tagged sequencing reads with tissue histology images to generate three-dimensional maps of chromatin state across an organ or tumor.

Sectoral value chain#

[Cryosection tissue preparation (10 µm)] ──> [In situ Tn5 transposition with spatial barcode] ──> [DNA library collection off slide]
                                                                                                              │
                     [Bioinformatic spatial reconstruction] <─── [High-throughput sequencing (NGS)] <┘

Value chain levels#

Cross-cutting technologies of the sector:

• Deterministic barcoding in tissue (DBiT-seq): flowing unique oligonucleotide barcodes through mutually perpendicular microchannels over a tissue section, generating a 2D coordinate grid at resolution down to 10 microns.
• Spatial Tn5 transposition: a modified Tn5 transposase that simultaneously fragments open chromatin and ligates adapters directly inside cell nuclei on a tissue section, rather than in a dissociated-cell suspension.
• Multiplexed spatial imaging platforms: commercial imaging-based spatial platforms (CosMx, MERFISH/MERSCOPE) that read thousands of RNA and protein targets directly on an intact tissue section at subcellular resolution.

02US#

The United States holds global leadership in patenting and commercializing spatial analysis systems, with major platform vendors headquartered domestically and funded by large federal genomics programs.

NanoString’s CosMx (now under Bruker), Vizgen’s MERFISH 2.0, EpiCypher’s CUT&Tag/CUT&RUN reagents#

• NanoString’s CosMx under Bruker Spatial Biology: following Bruker’s 2024 acquisition of NanoString’s spatial biology assets, the CosMx Spatial Molecular Imager achieved whole-transcriptome imaging at single-cell resolution and launched a 6,000-plex RNA assay, extending the platform’s reach from targeted panels toward genome-wide spatial profiling.
• Vizgen’s MERFISH 2.0 and OmniVue expansion: Vizgen launched MERFISH 2.0 chemistry and enhanced OmniVue panels with antibody-drug-conjugate (ADC) biomarker capability in 2026, alongside a spatial multi-omics roadmap unveiled at AGBT 2026 and new volumetric tissue-mapping capability presented at the Human Cell Atlas 2026 meeting.
• EpiCypher’s CUT&Tag/CUT&RUN reagent platform: EpiCypher supplies the CUTANA line of CUT&Tag and ChIC/CUT&RUN kits, SNAP-certified histone-mark antibodies, and multiomic CUT&RUN assays that many academic and commercial spatial-epigenome workflows build on for antibody-guided chromatin profiling.
• Federal research funding: large grants from the National Human Genome Research Institute (NHGRI) and the NIH’s Human Biomolecular Atlas Program (HuBMAP) fund much of the underlying spatial-omics method development.

03CN#

China has bet on independent, subcellular-resolution spatial sequencing hardware, anchored by BGI Group’s Stereo-seq platform, and applies spatial epigenomics to developmental and stem-cell atlases.

BGI’s Stereo-seq platform adapted for Spatial CUT&Tag, developmental atlas projects in Shanghai and Beijing#

• BGI’s Stereo-seq DNA nanoball chip platform: BGI Group’s Stereo-seq — spatially resolved transcriptomics on DNA nanoball chips — is being actively adapted for epigenetic applications (Spatial CUT&Tag), giving China a domestically developed alternative to the imaging-based US platforms.
• Developmental and stem-cell atlas projects: Chinese academic centers in Shanghai and Beijing use spatial epigenomics to build detailed embryo-development atlases and map plant stem-cell architecture, though independent 2025-2026 confirmation of a specific commercial vendor beyond BGI’s own platform could not be established within the current search — the domestic commercial-vendor landscape outside BGI is best described qualitatively pending stronger public disclosure.
• NMPA oversight: spatial diagnostic applications intersecting clinical use fall under China’s National Medical Products Administration framework, alongside the broader precision-medicine regulatory push.

04EU#

The European Union leads in developing bioinformatic algorithms for spatial alignment and multi-omic data integration, alongside emerging commercial spatial biology hardware makers.

Lunaphore’s COMET platform, EU standardization of sample-prep protocols, IVDR Class C oversight#

• Lunaphore’s COMET multiomics platform: the Swiss company’s COMET platform performs fully automated, same-section, high-throughput hyperplex spatial biology, positioned by the company as paving the way for spatial biology’s adoption in clinical research rather than research-only use.
• Protocol standardization push: European projects focus heavily on standardizing sample-preparation Standard Operating Procedures (SOPs), critical for reproducibility when spatial epigenomic results feed into clinical trials of new pharmaceutical candidates.
• IVDR Class C oversight: as spatial platforms move toward clinical diagnostic use, they fall under the EU’s In Vitro Diagnostic Regulation as Class C devices, requiring rigorous validation of reproducibility across sites and operators.

05Leading companies and research institutes#

06Tech stack and innovations#

1. Molecular stack and biological agents#

• Tn5 transposase: ultra-purified recombinant protein with high in situ DNA fragmentation and ligation activity.
• Validated histone-modification antibodies: monoclonal antibodies against H3K4me3 (active-promoter marker), H3K27me3 (silencing marker) and H3K27ac (active-enhancer marker).
• Diffusion modeling of Tn5 in tissue: predictive models of Tn5 concentration through the depth of a tissue section, accounting for effective diffusion through fixed cytoplasm and nuclear membrane along with first-order binding kinetics to open chromatin — used to optimize enzyme incubation time and concentration for uniform tagging depth.

2. Instrument stack and analytical equipment#

• High-throughput sequencers: Illumina NovaSeq 6000, MGI DNBSEQ-T7.
• Microfluidic barcoding stations: DBiT-seq-class platform systems with pressure control.
• High-precision cryostats: instruments such as the Leica CM3050 S for producing smooth, tear-free tissue sections.
• Integration software: Seurat’s Spatial module, Scanpy and Squidpy for joint spatial analysis of metabolic and epigenetic tracks.

07Value chains and production pipelines#

Industrial-laboratory pipeline for Spatial ATAC-seq#

┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. Freeze tissue in OCT &  │ ───> │ 2. Mount section & fix on  │
│    cryosection (10 µm)     │      │    poly-L-lysine slide     │
└───────────────────────────┘      └───────────────────────────┘
                                                 │
                                                 ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. Generate 2D barcode grid│ <─── │ 3. In situ Tn5 transposition│
│    via microfluidics        │      │    with oligo adapters      │
└───────────────────────────┘      └───────────────────────────┘
              │
              ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. Collect DNA library,    │ ───> │ 6. Bioinformatic coordinate │
│    PCR-amplify & sequence  │      │    mapping & visualization  │
└───────────────────────────┘      └───────────────────────────┘

Stage 1: Sample preparation

Fresh-frozen tumor tissue is embedded in OCT polymer medium and cut on a cryostat at -20°C into 10 µm-thick sections.

Stage 2: Fixation and permeabilization

Sections are mounted on specialized slides. Mild formaldehyde fixation followed by detergent treatment (Triton X-100) opens access for proteins to reach cell nuclei.

Stage 3: Chromatin transposition

Recombinant Tn5 transposase is applied to the section, penetrating cell nuclei and inserting adapters precisely at open, nucleosome-free DNA regions.

Stage 4: Coordinate barcoding

A polymer microfluidic chip is overlaid on the section. Barcode set A oligonucleotides (X coordinate) flow through a first channel system; the chip is then rotated 90 degrees and barcode set B (Y coordinate) is introduced through a second channel system with ligase.

Stage 5: Sequencing

DNA is released from the slide, purified on magnetic beads and PCR-amplified to prepare a library for high-throughput sequencing on Illumina or MGI instruments.

Stage 6: Methylome reconstruction

The bioinformatic pipeline maps sequenced DNA reads to the coordinate grid and visualizes the chromatin-accessibility map overlaid on the section’s histology photograph.