Chromatin accessibility profiling of targeted cell populations with laser capture microdissection coupled to ATAC-seq
Caterina Carraro, Lorenzo Bonaguro, Rachana Srinivasa, Martina van Uelft, Victoria Isakzai, Jonas Schulte-Schrepping, Prerna Gambhir, Tarek Elmzzahi, Jessica V. Montgomery, Hannah Hayer, Yuanfang Li, Heidi Theis, Michael Kraut, Krishnaa T. Mahbubani, Anna C. Aschenbrenner, Ireen König, Eugenio Fava, Hans‐Ulrich Fried, Elena De Domenico, Marc Beyer, Adem Saglam, Joachim L. Schultze
Abstract
Spatially resolved omics technologies reveal context-dependent cellular regulatory networks in tissues of interest. Beyond transcriptome analysis, information on epigenetic traits and chromatin accessibility can provide further insights on gene regulation in health and disease. Nevertheless, compared to the enormous advancements in spatial transcriptomics technologies, the field of spatial epigenomics is much younger and still underexplored. In this study, we report laser capture microdissection coupled to ATAC-seq (LCM-ATAC-seq) applied to fresh frozen samples for the spatial characterization of chromatin accessibility. We first demonstrate the efficient use of LCM coupled to in situ tagmentation and evaluate its performance as a function of cell number, microdissected areas, and tissue type. Further, we demonstrate its use for the targeted chromatin accessibility analysis of discrete contiguous or scattered cell populations in tissues via single-nuclei capture based on immunostaining for specific cellular markers.