InquirySingle-cell sequencing analysis provides a practical way to define cell types and states that can help understand normal cellular processes and the regulation of gene expression in various diseases. However, the process of tissue dissociation can lead to loss of spatial context and can also preferentially select certain cell types or perturb cell states due to dissociation or other environmental stresses. Spatial epigenomics has emerged to address these challenges, revolutionizing our understanding of gene regulation and cellular function. To investigate the mechanisms underlying the spatial organization of different cell types and functions in the tissue environment, it is necessary to examine not only gene expression but also the epigenetic basis, such as chromatin accessibility, in a spatially resolved manner. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) stands out as a powerful method for spatially resolved chromatin accessibility analysis, allowing direct spatial mapping of epigenetic states in tissue sections at the genomic scale and cellular level.
Technical Principle of Spatial ATAC-Seq
Spatial ATAC-seq is a method that combines in situ Tn5 (ATACsee) translocation chemistry and microfluidic deterministic barcoding to perform spatially resolved chromatin accessibility analysis on tissue sections. This method can be further applied to single cells. Microdissection of specific regions of tissue followed by scATAC-seq allows analysis of accessible chromatin in regions of interest.
Fig. 1. Chemistry workflow of spatial-ATAC-seq. (Deng Y, et al, 2021)
Workflow of the Spatial ATAC-Seq Technique
(1) Fresh frozen tissue sections are fixed to slides with barcodes and they are cross-linked to preserve chromatin structure during the immunostaining process.
(2) Imaging of immunostained sections is performed to record tissue coordinates and protein expression data.
(3) Tn5 translocation is performed directly in permeabilized sections to label open chromatin.
(4) DNA tags were hybridized to spatial barcode surface oligonucleotides during gentle tissue digestion with the help of chimeric splint oligonucleotides.
(5) Ligation to the splint and subsequent polymerase gap filling and extension generates open chromatin fragments with spatial barcodes and PCR handles for generating sequencing libraries.
Fig. 2. Spatial-ATAC-seq: design, workflow, and data quality. (Deng Y, et al, 2021)
Our Spatial ATAC-Seq Analysis Service
CD Genomics offers a comprehensive spatial ATAC-seq analysis service using state-of-the-art laboratory facilities and bioinformatics expertise to enable spatially resolved chromatin accessibility analysis in tissue sections. Our team of dedicated scientists is committed to providing accurate, high-quality results to meet the diverse needs of researchers across a wide range of disciplines. With our advanced technology and meticulous workflow, we enable researchers to reveal spatially epigenomic landscapes with unprecedented resolution and detail.
Advantages of Our Service
Cutting-edge Methodology
CD Genomics uses the latest Spatial ATAC-Seq method, which allows spatially resolved analysis of chromatin accessibility in tissue sections and provides valuable insights into the regulation of gene expression in a spatial context.
High-quality Data Generation
We adhere to strict quality control measures throughout the experimental process to ensure accurate and reproducible results. From sample preparation to data generation, our team follows standardized protocols to minimize technical variation and optimize data quality.
Multiple Tissue Types Can be Analyzed
High-quality data can be generated for many tissue types, including spleen, brain, melanoma, PDX, kidney, etc.
Advanced Bioinformatics Analysis
CD Genomics specializes in bioinformatics analysis, employing cutting-edge algorithms and software tools to extract meaningful insights from complex spatial ATAC-Seq data. Our bioinformatics team has extensive experience in processing and analyzing large-scale genomic datasets, enabling us to identify differentially accessible chromatin regions, discover regulatory elements, and reveal spatial gene expression patterns.
Sample Requirements
Tissue sections: Fresh frozen tissue sections are preferred for spatial ATAC-Seq analysis. Tissue sections should be of sufficient thickness to allow effective transposase accessibility and capture of chromatin fragments.
Sample preservation: Proper preservation of tissue sections is essential to maintain the structural integrity of chromatin. Cross-linking or fixation methods can be used to preserve the spatial organization of chromatin and allow for subsequent immunostaining or imaging.
Cellularity: The selection of tissue sections should take into account the cellular composition and heterogeneity within the sample. It is important to ensure that the cell type of interest is sufficiently representative to capture meaningful spatial chromatin accessibility features.
Application Areas
Developmental Biology
Our spatial ATAC-seq service can reveal the epigenetic landscape during embryonic development and organogenesis. By mapping chromatin accessibility patterns in developing tissues, we can identify tissue region-specific epigenetic landscapes, discover gene regulatory networks, and gain insight into the molecular mechanisms that control tissue development.
Neurobiology
Our spatial ATAC-seq service allows the mapping of available genomic regions in different brain regions and cell types, helping to identify key regulators involved in neurogenesis, neuronal differentiation, and synaptic plasticity.
Disease Pathogenesis
Our spatial ATAC-seq service can reveal spatial epigenetic alterations associated with a variety of diseases, including cancer, neurological disorders, and immune-related diseases. By examining the accessibility characteristics of chromatin in disease-affected tissues, researchers can identify aberrant regulatory elements, potential disease drivers, and novel therapeutic targets.
Tissue Microenvironment
Our spatial ATAC-seq service enables the study of immune cell organization in lymphoid follicles, spatially distinct cell types in various tissues, and the interactions between different cell populations within tissues.
With its cutting-edge analytical services, CD Genomics ensures accurate and comprehensive analysis of spatial ATAC-seq data. By leveraging this innovative technology, we can help you unlock the spatial epigenomic landscape, leading to breakthrough discoveries in developmental biology, neurobiology, disease pathogenesis, and tissue microenvironment research. If you are interested in our services, please contact us now.
References
- Deng Y, Bartosovic M, Ma S, et al. Spatial-ATAC-seq: spatially resolved chromatin accessibility profiling of tissues at genome scale and cellular level[J]. bioRxiv, 2021: 2021.06. 06.447244.
- Llorens-Bobadilla E, Zamboni M, Marklund M, et al. Solid-phase capture and profiling of open chromatin by spatial ATAC[J]. Nature Biotechnology, 2023: 1-4.
