ATACSeq of TET2-mutant human neutrophils

Somatic mutations acquired by hematopoietic stem cells (HSCs) are commonly found over the course of a lifespan. Some of these clones will outgrow through a process known as clonal hematopoiesis (CH) and produce mutated immune cell progeny, which will shape host immunity. Individuals with CH are asymptomatic but have increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections. Despite the key role that neutrophils play in the development of such diseases, little is known about how these prevalent somatic mutations affect neutrophil functionality. In this work, we describe how mutations in TET2, one of the most common mutated genes in individuals with CH, affect human neutrophil biology. Using CRISPR-mediated genetic engineering of human HSCs and transplantation in immunodeficient mice, we have sorted and analyzed the chromatin conformation of TET2 mutant (TET2Mut) neutrophils coming from 4 biological replicates.