Type: Molecular / Cellular,

Keywords: Epigenomic, Single cell profiling, Non-neuronal cell taxonomy atlas, BICCN, BRAIN Initiative

Spatially-mapped single-cell epigenomic profiles

single-cell combinatorial indexing on Microbiopsies Assigned to Positions for the Assay for Transposase Accessible Chromatin (sciMAP-ATAC). High-throughput single cell genomic assays resolve the heterogeneity of cell states in complex tissues, however, the spatial orientation within the network of interconnected cells is lost. We present a novel method for capturing spatially-resolved epigenomic profiles of single cells within intact tissue, and apply this method to generate non-neuronal cell taxonomy atlases of human and mouse cortex. This method will be made accessible through and all data, along with single cell analyses, will be made available through the BRAIN Initiative Cell Census Network (BICCN)

* Highly-scalable spatially-resolved single-cell profiling of chromatin states
* Generates thousands of spatially-resolved high quality single-cell ATAC-seq libraries
* Acquires spatially resolved epigenomic single-cell data with the use of immediately available commercial tools
* Rapid subsetting of cells by localization and mapping of cells across vector space in 3D
* Can be applied to any single-cell combinatorial indexing technique to enable spatially-registered single-cell genome, transcriptome, chromatin folding, or methylation assays

* Applied in the adult mouse and human cortex to discriminate cortical layering of glutamatergic neurons and establish the spatial ordering of single cells within intact tissue
* Assessed layer-specific marker gene chromatin accessibility and transcription factor motif enrichment
* Applied to mouse stroke model to characterize the spatially progressive phenotypes that vary by proximity to the ischemic infarction core with cell type specificity

* High-density microbiopsy sampling, ranging from 100-500 μm in diameter, on cryosectioned tissue slices, between 100-300 μm in thickness
* Used to profile the murine somatosensory cortex, recapitulating known marker gene progression through cortical layering and cell type composition based on the category and positioning of spatially-registered microbiopsy punches

* Low-cost
* Highly-scalable
* Does not require specialized equipment
* Scales nonlinearly, enabling high throughput potential
* Hypothesis-independent approach
* Translatable to any tissue, culture, or model system which can be cryosectioned
* Preserves cellular localization within intact tissues

* Thornton, C. A., Mulqueen, R. M., Nishida, A., Torkenczy, K. A., Lowenstein, E. G., Fields, A. J., Steemers, F.J., Zhang, W., McConnell, H. L., Woltjer, R. J., Mishra, A., Wright, K. M., Adey, A. C. (2021). Spatially mapped single-cell chromatin accessibility. Nature Communications.

* Technology Preprint:

* Published Protocol:


Casey Thornton (ACGME Laboratory Genetics & Genomics Fellow)
Andrew Adey (Principal Investigator)


Oregon Health and Science University



* BRAIN Initiative, National Institute of Drug Abuse, National Institutes of Health, grant number 1R01DA047237-01

*  American Association of University Women (AAUW)