Multi-modal single-cell sequencing reveals new features in peripheral circulating monocytes in trauma patients aligns with fast recovery 2936

Description Previous transcriptomic studies revealed a dramatic upregulation of inflammation and simultaneously downregulation of MHCII and IFN signaling pathways after trauma which gradually return to baseline. The magnitude of these changes is associated with differential prognosis. In this study, we applied DOGMA-seq (RNA + ATAC + ADT) on the peripheral blood mononuclear cells from 16 trauma patients undergoing slow or fast recovery (ICU days >7 vs. < 7 days), along with 4 age and sex matched healthy controls. We identified a new signature in monocytes which is induced after trauma. In contrast to the previous paradigm, this signature is not simply a gradual return to the baseline state. Instead, it continuously increases along timeline, especially in the patients undergoing a fast-recovery trajectory. Taking advantage of a published whole blood transcriptomic dataset of 167 trauma patients, this signature significantly associates with a better prognosis by ∼ 1 day after injury. Gene set enrichment analysis shows this signature is associated with wound healing and tissue repair. ATAC-seq data reveals distinct open chromatin status associated with this signature. This study extends the current paradigm of trauma immune response by adding another dimension, a favorable signal induced by traumatic injury and possible associated with long-term epigenetic changes. Further investigation into how to boost this signal may provide new strategy to improve the outcome of trauma patients. Funding Sources R35GM127027 Topic Categories Computational and Systems Immunology (COMP)