Kfoury YS, Ji F, Mazzola M, Sykes DB, Scherer AK, Anselmo A, Akiyama Y, Mercier F, Severe N, Kokkaliaris KD, Zhao T, Brouse T, Saez B, Seidl J, Papazian A, Ivanov P, Mansour MK, Sadreyev RI, Scadden DT.Cell Stem Cell. 2021 Dec 2;28(12):2090-2103.e9. doi: 10.1016/j.stem.2021.08.014. Epub 2021 Sep 21.PMID: 34551362
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.