Gen Biotechnology

Improved Cell-Type Identification and Comprehensive Mapping of Regulatory Features with Spatial Epigenomics 96-Channel Microfluidic Platform

Zev Kartiganer, Gumaro Rojas, Machele Riccio, Abigail Tyree, Katelyn Noronha, Molly Wetzel, Joshua Barnett, James McGann, Jennifer Garbarino, Daniel Massucci, Nouroddin Sotoudeh Chafi, Silas Decker, Arianna McDaniels, Jeffrey Sabina, David Levchenko, Jose Perez, Colin Ng, and Kenneth Wang

Abstract

Gene expression is subject to epigenetic regulation and is dependent upon cellular context. Spatial omics tools can provide insight into cellular context; however, development has centered on spatial transcriptomics and proteomics. Deterministic barcoding in tissue for spatial omics sequencing was the first spatial epigenomics platform at the cellular level. In this study, we present a comparison of spatial epigenomic profiling on both 50-channel and 96-channel platforms. The new 96-channel microfluidics chip design greatly improved precision in cell typing and identification of regulatory elements by spatial-ATAC-seq. Spatial mapping reveals complexity of glial cell and neuronal localization within brain structures as well as cis-regulatory elements controlling cellular function. This technology streamlines spatial analysis of the epigenome and contributes a new layer of spatial omics to uncover the context-dependent regulatory mechanisms underpinning development, disease, and normal cellular function.