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. 2021. tiRNA signaling via stress-regulated vesicle transfer in the hematopoietic niche. Cell stem cell. 28(12):2090-2103.e9. Pubmed: 34551362 DOI:10.1016/j.stem.2021.08.014


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.
Copyright © 2021 Elsevier Inc. All rights reserved.

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David Scadden’s laboratory is dedicated to discovering the principles governing blood cell production, with the ultimate goal of guiding the development of therapies for blood disorders and cancer.

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