{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:27:32Z","timestamp":1790270852198,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["4R00HL121076\u201003"],"award-info":[{"award-number":["4R00HL121076\u201003"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01HL143967"],"award-info":[{"award-number":["1R01HL143967"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Splenic hematopoiesis is crucial to the pathogenesis of diseases including myocardial infarction and atherosclerosis. The spleen acts as a reservoir of myeloid cells, which are quickly expelled out in response to acute inflammation. In contrast to the well\u2010defined bone marrow hematopoiesis, the cellular and molecular components sustaining splenic hematopoiesis are poorly understood. Surprisingly, we found that, unlike quiescent bone marrow hematopoietic stem cells (\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    ), most of splenic\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    are in the G1 phase in C57\n                    <jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\n                    \/6 mice. Moreover, splenic\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    were enriched for genes involved in G0\u2010G1 transition and expressed lower levels of genes responsible for G1\u2010S transition. These data indicate that, at steady state, splenic\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    are pre\u2010activated, which may expedite their cell cycle entry in emergency conditions. Consistently, in the acute phase of septic shock induced by\n                    <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\n                    injection, splenic\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    entered the S\u2010G2\u2010M phase, whereas bone marrow\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    did not. Mobilization and transplantation experiments displayed that bone marrow\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    , once in the spleen, acquired cell cycle status similar to splenic\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    , strongly suggesting that the splenic microenvironment plays an important role in\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    pre\u2010activation. In addition, we found that myeloid translocation gene 16 (\n                    <jats:italic>Mtg16<\/jats:italic>\n                    ) deficiency in C57\n                    <jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\n                    \/6 mice resulted in significantly increased S\u2010G2\u2010M entry of splenic but not bone marrow\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    , suggesting that Mtg16 is an intrinsic negative regulator of G1\u2010S transition in splenic\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    . Altogether, this study demonstrates that compared to bone marrow, splenic\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    are in a pre\u2010activated state, which is driven by extracellular signals provided by splenic microenvironment and\n                    <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>\n                    intrinsic factor Mtg16.\n                  <\/jats:p>","DOI":"10.1111\/imcb.12035","type":"journal-article","created":{"date-parts":[[2018,3,11]],"date-time":"2018-03-11T01:36:33Z","timestamp":1520732193000},"page":"772-784","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Splenic hematopoietic stem cells display a pre\u2010activated phenotype"],"prefix":"10.1111","volume":"96","author":[{"given":"Emilie","family":"Coppin","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Medicine Vascular Medicine Institute University of Pittsburgh Medical Center BST 1720.1, 200 Lothrop Street Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Florentin","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Vascular Medicine Institute University of Pittsburgh Medical Center BST 1720.1, 200 Lothrop Street Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathish Babu","family":"Vasamsetti","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Vascular Medicine Institute University of Pittsburgh Medical Center BST 1720.1, 200 Lothrop Street Pittsburgh PA 15213 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anagha","family":"Arunkumar","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine Vascular Medicine Institute University of Pittsburgh 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