Oncogene-induced senescence in hematopoietic progenitors features myeloid restricted hematopoiesis, chronic inflammation and histiocytosis

We generated a humanized mouse model of oncogene-induced senescence in hematopoietic stem and progenitor cells by expressing the activated oncogene BRAF-V600E. Mice succumbed to bone marrow failure and multi-organ dissemination of aberrant macrophages and dendritic cells. We observed a myeloid-restricted hematopoiesis,and uncovered the activation of a senescence program, characterized by growth arrest and senescence-associated secretory phenotype (SASP), which involved also non-mutated bystander cells. Overall design: We sequenced the mRNA of FACS-sorted human CD45+CD33+ cells from the bone marrow of NSG mice transplanted with CD34+ cells transduced with lentiviral vectors expressing BRAF-V600E and GFP, wtBRAF and GFP, GFP alone and mock control