Extracellular vesicles (EVs) transfer complex biologic material between cells. However, the role of this process in vivo is poorly defined. Here, we demonstrate that osteoblastic cells in the bone marrow (BM) niche elaborate extracellular vesicles that are taken up by hematopoietic progenitor cells in vivo. Genotoxic or infectious stress rapidly increased stromal-derived extracellular vesicle transfer to granulocyte-monocyte progenitors. The extracellular vesicles contained processed tRNAs (tiRNAs) known to modulate protein translation. 5′-ti-Pro-CGG-1 was preferentially abundant in osteoblast-derived extracellular vesicles and, when transferred to granulocyte-monocyte progenitors, increased protein translation, cell proliferation, and myeloid differentiation. Upregulating EV transfer improved hematopoietic recovery from genotoxic injury and survival from fungal sepsis. Therefore, EV-mediated tiRNA transfer provides a stress-modulated signaling axis in the BM niche distinct from conventional cytokine-driven stress responses.

细胞外囊泡 (EV) 在细胞之间转移复杂的生物物质。然而，这一过程在体内的作用尚不清楚。在这里，我们证明骨髓（BM）生态位中的成骨细胞精心制作细胞外囊泡，这些囊泡被体内造血祖细胞吸收。基因毒性或感染应激迅速增加了基质来源的细胞外囊泡向粒细胞-单核细胞祖细胞的转移。细胞外囊泡含有已知可调节蛋白质翻译的加工过的 tRNA (tiRNA)。 5'-ti-Pro-CGG-1 在成骨细胞衍生的细胞外囊泡中优先丰富，当转移到粒细胞-单核细胞祖细胞时，会增加蛋白质翻译、细胞增殖和骨髓分化。上调 EV 转移可改善基因毒性损伤的造血恢复和真菌败血症的存活率。因此，EV介导的tiRNA转移在BM生态位中提供了与传统细胞因子驱动的应激反应不同的应激调节信号轴。