Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland; Geneva Center for Inflammation Research, Geneva, Switzerland; Translational Research Center for Oncohematology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Ziyang Su
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland; Geneva Center for Inflammation Research, Geneva, Switzerland; Translational Research Center for Oncohematology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Tania Wyss
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland; Geneva Center for Inflammation Research, Geneva, Switzerland; Translational Data Science Facility, AGORA Cancer Research Center, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland; Translational Research Center for Oncohematology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Giuseppe Ercolano
Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy
Sara Trabanelli
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland; Geneva Center for Inflammation Research, Geneva, Switzerland; Translational Research Center for Oncohematology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Camilla Jandus
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland; Geneva Center for Inflammation Research, Geneva, Switzerland; Translational Research Center for Oncohematology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Corresponding author
Summary: Innate lymphoid cells (ILCs) are plastic immune cells divided into 3 main subsets, characterized by distinct phenotypic and functional profiles. Using single cell approaches, heightened heterogeneity of mouse ILCs has been 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 and diverse chromatin accessibility within main ILC populations, compatible with differentially poised states. We validate the use of this healthy donor-based analysis as resource dataset to help inferring ILC changes occurring in disease conditions. Overall, our work provides insights in the complex human ILC biology. We anticipate it to facilitate hypothesis-driven studies in patients, without the need to perform single cell OMICs using precious patients’ material.
