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.

本研究通过表达激活型癌基因BRAF-V600E，构建了造血干细胞与祖细胞中癌基因诱导衰老的人源化小鼠模型。小鼠因骨髓衰竭以及异常巨噬细胞与树突状细胞的多器官播散而死亡。我们观察到髓系限制性造血现象，并揭示了衰老程序的激活：该程序以生长停滞及衰老相关分泌表型（SASP）为特征，且波及未发生突变的旁观者细胞。