ArticleCell stem cell2021
tiRNA signaling via stress-regulated vesicle transfer in the hematopoietic niche.
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Article in Cell stem cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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33citing papers in PubMed
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33 citing papers in PubMed.
- tRNA‑derived RNAs in hepatic diseases: From biological functions to clinical translation (Review).International journal of molecular medicine · 2026Review
- The Role of EVs in the Aging Hematopoietic System.Aging cell · 2026Review
- tRNA-derived small RNAs in tumor microenvironment remodeling: From mechanistic insights to therapeutic perspectives.Oncogene · 2026Review
- HIV-1 Nef generates lasting innate immune memory in haematopoietic stem and progenitor cells in vivo.EMBO reports · 2026Article
- tRNA modifications in cancer: from molecular mechanisms to clinical translation.Biomarker research · 2026Review
- Niche-derived exosomes controlFrontiers in immunology · 2026Article
- Niche-generated taurine is leukemic fuel.Cell research · 2025Article
- Mechanisms of Transfer RNA Fragments Functionality Within and Between Cells and Organisms.Cells · 2025Review
- tRF-5004b Enriched Secretory Autophagosomes Induce Endothelial Cell Activation to Drive Acute Respiratory Distress Syndrome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Weight of time: exploring the link between obesity and aging.Aging clinical and experimental research · 2025Review
- RNase L produces tRNA-derived RNAs that contribute to translation inhibition.RNA (New York, N.Y.) · 2025Article
- Preventing MSC aging and enhancing immunomodulation: Novel strategies for cell-based therapies.Regenerative therapy · 2025Review
- tRNA-derived fragments: biomarkers and therapeutic targets in autoimmune diseases.Immunologic research · 2025Review
- Bone marrow mesenchymal stromal cells support translation in refractory acute myeloid leukemia.Cell reports · 2025Article
- Targeting tRNA-Derived Non-Coding RNA Alleviates Diabetes-Induced Visual Impairment through Protecting Retinal Neurovascular Unit.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- tRNA-derived small RNAs in disease immunity.Theranostics · 2025Review
- How aging influences the gut-bone marrow axis and alters hematopoietic stem cell regulation.Heliyon · 2024Review
- Full-length tRNAs lacking a functional CCA tail are selectively sorted into the lumen of extracellular vesicles.bioRxiv : the preprint server for biology · 2024Article
- Roles and regulation of tRNA-derived small RNAs in animals.Nature reviews. Molecular cell biology · 2024Review
- Oxidative Stress, Transfer RNA Metabolism, and Protein Synthesis.Antioxidants & redox signaling · 2024Review
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Authors and funding
19 authors.
Youmna S KfouryCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: youmna.kfoury@gmail.com.
Fei JiDepartment of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Michael MazzolaCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
David B SykesCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Allison K SchererDivision of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
Anthony AnselmoDepartment of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Yasutoshi AkiyamaDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Francois MercierCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Nicolas SevereCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Konstantinos D KokkaliarisCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Ting ZhaoCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Thomas BrouseCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Borja SaezCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Jefferson SeidlCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Ani PapazianCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Pavel IvanovDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Harvard Initiative for RNA Medicine, Boston, MA 02115, USA.
Michael K MansourHarvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Ruslan I SadreyevDepartment of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
David T ScaddenCenter for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Harvard Stem Cell Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA. Electronic address: david_scadden@harvard.edu.
Funding
Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3MROLE OF DIETARY CONSTITUENTS ON GENE EXPRESSION IN INTESTINAL EPITHELIUMP30DK040561 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Takara Leah Stanley · 1994 to 2026
$31.6MTransgenic CoreP30DK057521 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI KAHN, BARBARA B. · 2000 to 2019
$31.4MSkeletal Phenotyping CoreP30AR066261 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI KRONENBERG, HENRY M. · 2014 to 2018
$3.5MDeconvoluting the hematopoietic niche under stressR01DK107784 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI KHARCHENKO, PETER V, SCADDEN, DAVID T · 2016 to 2019
$2.1MBiology of RNA G-quadruplexesR01GM126150 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI IVANOV, PAVEL · 2019 to 2023
$1.9MtRNA-derived stress-induced RNAs and translational controlR01GM146997 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI IVANOV, PAVEL · 2022 to 2025
$1.6MImageStream X Analyzer 2011S10OD012027 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2012 to 2012
$595kNIAMS NIH HHS P30 AR066261NIDDK NIH HHS P30 DK040561NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30 DK057521NIDDK NIH HHS R01 DK107784NIGMS NIH HHS R01 GM126150NIGMS NIH HHS R01 GM146997NIH HHS S10 OD012027
Abstract
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.
Indexed as
Extracellular VesiclesHematopoietic Stem CellsBone MarrowBone Marrow CellsHematopoiesisbone marrowextracellular vesicleshematopoiesismyeloid progenitorsnicheprotein translationsignalingtiRNAs
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