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

Youmna S. Kfoury, Fei Ji, Michael Mazzola, David B. Sykes, Allison K. Scherer, Anthony Anselmo, Yasutoshi Akiyama, Francois Mercier, Nicolas Severe, Konstantinos D. Kokkaliaris, Ting Zhao, Thomas Brouse, Borja Saez, Jefferson Seidl, Ani Papazian, Pavel Ivanov, Michael K. Mansour, Ruslan I. Sadreyev, David T. Scadden

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2090-2103.e9
JournalCell Stem Cell
Issue number12
Publication statusPublished - 2021 Dec 2
Externally publishedYes


  • bone marrow
  • extracellular vesicles
  • hematopoiesis
  • myeloid progenitors
  • niche
  • protein translation
  • signaling
  • tiRNAs

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology


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