Dynamic single-cell regulomes characterize human peripheral blood ILC subpopulations [scATAC-seq]
Innate lymphoid cells (ILCs) are highly plastic immune cells that have been separated into 3 main subsets, characterized by distinct phenotypic and functional profiles. Using single cell approaches, heightened heterogeneity of mouse ILCs has been recently appreciated, imprinted by tissue signals that shape their transcriptome and epigenome. Intra-subset diversity has also been observed in human ILCs. However, combined transcriptomic and epigenetic analyses of single ILCs in humans are lacking.  Here we show high transcriptional and epigenetic heterogeneity among human circulating ILCs in healthy individuals. We describe phenotypically distinct subclusters within main circulating ILC populations. We show diverse chromatin accessibility within main ILC subsets, compatible with differentially poised states. We validate the use of this healthy donor-based analysis as resource dataset to infer ILC changes occurring in disease conditions. Overall, our work provides new insights in the complex human ILC biology. We anticipate our work to be a starting point to facilitate hypothesis-driven studies in patients, without the need to perform single cell OMICs using precious patients' material Overall design: We sorted total innate lymphoid cells from peripheral blood of 3 healthy human donors, and subjected them to single-cell ATAC sequencing analysis using the 10x Genomics technology