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


Posted: 2021-09-22 19:00:00
Cell Stem Cell . 2021 Sep 15;S1934-5909(21)00351-9. doi: 10.1016/j.stem.2021.08.014. Online ahead of print. Youmna S Kfoury 1 , Fei Ji 2 , Michael Mazzola 3 , David B Sykes 3 , Allison K Scherer 4 , Anthony Anselmo 2 , Yasutoshi Akiyama 5 , Francois Mercier 3 , Nicolas Severe 3 , Konstantinos D Kokkaliaris 3 , Ting Zhao 3 , Thomas Brouse 3 , Borja Saez 3 , Jefferson Seidl 3 , Ani Papazian 3 , Pavel Ivanov 6 , Michael K Mansour 7 , Ruslan I Sadreyev 8 , David T Scadden 9 Affiliations Expand Affiliations 1 Center 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. 2 Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. 3 Center 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. 4 Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA. 5 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. 6 Division 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. 7 Harvard 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. 8 Department 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. 9 Center 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. Item in Clipboard Youmna S Kfoury et al. Cell Stem Cell. 2021. Show details Display options Display options Format Cell Stem Cell . 2021 Sep 15;S1934-5909(21)00351-9. doi: 10.1016/j.stem.2021.08.014. Online ahead of print. Authors Youmna S Kfoury 1 , Fei Ji 2 , Michael Mazzola 3 , David B Sykes 3 , Allison K Scherer 4 , Anthony Anselmo 2 , Yasutoshi Akiyama 5 , Francois Mercier 3 , Nicolas Severe 3 , Konstantinos D Kokkaliaris 3 , Ting Zhao 3 , Thomas Brouse 3 , Borja Saez 3 , Jefferson Seidl 3 , Ani Papazian 3 , Pavel Ivanov 6 , Michael K Mansour 7 , Ruslan I Sadreyev 8 , David T Scadden 9 Affiliations 1 Center 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. 2 Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. 3 Center 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. 4 Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA. 5 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. 6 Division 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. 7 Harvard 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. 8 Department 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. 9 Center 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. Item in Clipboard CiteDisplay options Display options Format 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. Keywords: bone marrow; extracellular vesicles; hematopoiesis; myeloid progenitors; niche; protein translation; signaling; tiRNAs. Copyright © 2021 Elsevier Inc. All rights reserved. Conflict of interest statement Declaration of interests D.T.S. is a director, co-founder, and shareholder of Magenta Therapeutics, Clear Creek Bio, and LifeVaultBio; a director and shareholder of Agios Pharmaceuticals and Editas Medicines; and a co-founder and a shareholder of Fate Therapeutics. D.B.S. is a scientific founder and shareholder in Clear Creek Bio. [x] Cite Copy Format: Send To [x]

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バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
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