Cell-intrinsic effects of clonal hematopoiesis in heart failure

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is caused by somatic mutations in hematopoietic stem cells and associates with worse prognosis patients heart failure. Patients harboring CHIP show enhanced inflammation. However, whether these signatures are derived from the relatively low number or indicators systemic pro-inflammatory activation that associated unclear. Here we assess cell-intrinsic effects mutant Using an improved single-cell sequencing pipeline (MutDetect-Seq), DNMT3A monocytes, CD4+ T NK exhibit altered gene expression profiles. While monocytes showed increased genes inflammation phagocytosis, present effector functions. Increased paracrine signaling pathways predicted validated between wild-type cells, which amplify inflammatory circuits. Altogether, data provide novel insights into how might promote a