tiRNA signaling via stress-regulated vesicle transfer in the hematopoietic niche

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.

Automated summary

The study demonstrates that osteoblastic cells in the bone marrow niche secrete extracellular vesicles containing tiRNAs that can be transferred to hematopoietic progenitor cells, impacting protein translation, cell proliferation, and myeloid differentiation. This transfer of EVs improves hematopoietic recovery from genotoxic injury and survival from fungal sepsis, suggesting a stress-modulated signaling axis in the bone marrow microenvironment distinct from conventional cytokine-driven responses.