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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,11,29]]},"abstract":"<jats:p>\n                    Platelets play a role not only in hemostasis and thrombosis, but also in inflammation and innate immunity. We previously reported that an activated form of tyrosyl-tRNA synthetase (YRS\n                    <jats:sup>ACT<\/jats:sup>\n                    ) has an extratranslational activity that enhances megakaryopoiesis and platelet production in mice. Here, we report that YRS\n                    <jats:sup>ACT<\/jats:sup>\n                    mimics inflammatory stress inducing a unique megakaryocyte (MK) population with stem cell (Sca1) and myeloid (F4\/80) markers through a mechanism dependent on Toll-like receptor (TLR) activation and type I interferon (IFN-I) signaling. This mimicry of inflammatory stress by YRS\n                    <jats:sup>ACT<\/jats:sup>\n                    was studied in mice infected by lymphocytic choriomeningitis virus (LCMV). Using Sca1\/EGFP transgenic mice, we demonstrated that IFN-I induced by YRS\n                    <jats:sup>ACT<\/jats:sup>\n                    or LCMV infection suppressed normal hematopoiesis while activating an alternative pathway of thrombopoiesis. Platelets of inflammatory origin (Sca1\/EGFP\n                    <jats:sup>+<\/jats:sup>\n                    ) were a relevant proportion of those circulating during recovery from thrombocytopenia. Analysis of these \u201cinflammatory\u201d MKs and platelets suggested their origin in myeloid\/MK-biased hematopoietic stem cells (HSCs) that bypassed the classical MK-erythroid progenitor (MEP) pathway to replenish platelets and promote recovery from thrombocytopenia. Notably, inflammatory platelets displayed enhanced agonist-induced activation and procoagulant activities. Moreover, myeloid\/MK-biased progenitors and MKs were mobilized from the bone marrow, as evidenced by their presence in the lung microvasculature within fibrin-containing microthrombi. Our results define the function of YRS\n                    <jats:sup>ACT<\/jats:sup>\n                    in platelet generation and contribute to elucidate platelet alterations in number and function during viral infection.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2212659119","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T15:18:11Z","timestamp":1669043891000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["Inflammatory platelet production stimulated by tyrosyl-tRNA synthetase mimicking viral infection"],"prefix":"10.1073","volume":"119","author":[{"given":"Yosuke","family":"Morodomi","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, MERU-Roon Research Center on Vascular Biology, The Scripps Research Institute, La Jolla, CA 92037"},{"name":"The Scripps Laboratories for tRNA Synthetase Research, Department of Molecular Medicine, The Scripps 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92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2554-084X","authenticated-orcid":false,"given":"Xiang-Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"The Scripps Laboratories for tRNA Synthetase Research, Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6064-2166","authenticated-orcid":false,"given":"Wolfram","family":"Ruf","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, 55128 Germany"},{"name":"Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Schimmel","sequence":"additional","affiliation":[{"name":"The Scripps Laboratories for tRNA Synthetase Research, 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