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An immune-cell signature of bacterial sepsis (Bone marrow stimulation)
Miguel Reyes, Michael R. Filbin, Roby P. Bhattacharyya, Kianna Billman, Thomas Eisenhaure, Deborah T. Hung, Bruce D. Levy, Rebecca M. Baron, Paul C. Blainey, Marcia B. Goldberg and Nir Hacohen
Dysregulation of the immune response to bacterial infection can lead to sepsis, a condition with high mortality. Multiple whole-blood gene-expression studies have defined sepsis-associated molecular signatures, but have not resolved changes in transcriptional states of specific cell types. Here, we used single-cell RNA-sequencing to profile the blood of people with sepsis (n= 29) across three clinical cohorts with corre-sponding controls (n= 36). We profiled total peripheral blood mononuclear cells (PBMCs, 106,545 cells) and dendritic cells (19,806 cells) across all subjects and, on the basis of cluster-ing of their gene-expression profiles, defined 16 immune-cell states. We identified a unique CD14+ monocyte state that is expanded in people with sepsis and validated its power in dis-tinguishing these individuals from controls using public tran-scriptomic data from subjects with different disease etiologies and from multiple geographic locations (18 cohorts, n= 1,467 subjects). We identified a panel of surface markers for isolation and quantification of the monocyte state and characterized its epigenomic and functional phenotypes, and propose a model for its induction from human bone marrow. This study demonstrates the utility of single-cell genomics in discovering dis-ease-associated cytologic signatures and provides insight into the cellular basis of immune dysregulation in bacterial sepsis.