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High Capacity Sample Multiplexing for Chromatin Accessibility Profiling Within Single Cells

ABSTRACT: Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel approach, sciPlex-ATAC-seq, which uses unmodified DNA oligos as sample-specific nuclear labels, enabling the concurrent profiling of chromatin accessibility within single nuclei from virtually unlimited specimens or experimental conditions. We first demonstrate our method with a chemical epigenomics screen, in which we identify drug-altered distal regulatory sites predictive of compound- and dose-dependent effects on transcription. We then analyze cell type-specific chromatin changes in PBMCs from multiple donors responding to synthetic and allogeneic immune stimulation. We quantify stimulation-altered immune cell compositions and isolate the unique effects of allogeneic stimulation on chromatin accessibility specific to T-lymphocytes. Finally, we observe how various immunosuppressive compounds disrupt canonical allogeneic activation of resting T-cells through chromatin.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE178953 | GEO | 2023/03/05

REPOSITORIES: GEO

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