Effect of IL-1a on WT or Tet2+/- HSCs. RNA sequencing of WT and Tet2+/- HSCs exposed to PBS or IL-1a

Clonal hematopoiesis of indeterminate potential (CHIP) associates with advanced age and increased risk for hematological malignancy, cardiovascular disease and all-cause mortality. Loss-of-function somatic mutations in TET2 are frequent drivers of CHIP. However, the contribution of ageing-associated cooperating cell-extrinsic drivers, like inflammation, remains unexplored. Using bone marrow (BM) transplantation and genetic mosaicism mouse models of Tet2+/- driven CHIP, we identified the IL-1 pathway as a relevant and therapeutically targetable driver of CHIP progression during ageing. In this project, we want to characterize the transcriptomic changes in wild-type (WT) or Tet2+/- hematopoietic stem cells (HSCs) upon chronic exposure to IL-1a.