Poster #083, City of Hope
Modeling TET2 clonal hematopoiesis-associated cardiac dysfunction using human iPSCs
Mentors: Vertica Agnihotri, PhD, PI: June-Wha Rhee, MD
Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of mutated hematopoietic stem cells, is associated with an increased risk of cardiovascular disease (CVD). Mutations in the epigenetic regulator TET2 are among the most common in CHIP and have been associated with increased inflammation and cardiovascular dysfunction. This study uses human induced pluripotent stem cells (iPSC), macrophages (iMACs), and cardiomyocytes to investigate the effects of TET2knockout (TET2KO) on cellular behavior and function. We hypothesize that TET2KO macrophages will exhibit a hyperinflammatory phenotype and negatively affect cardiomyocyte contractile function. Inflammatory and metabolic changes will be assessed through cellular characterization and functional assays. Additionally, macrophage-cardiomyocyte coculture models will be used to examine how TET2-driven alterations influence overall cardiac health. By modeling CHIP using a human iPSC system, this research aims to improve the understanding of biological mechanisms that link TET2 mutations to CVD development and disease progression.