{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:33:25Z","timestamp":1789450405974,"version":"build-2803163510"},"reference-count":54,"publisher":"National Academy of Sciences","issue":"38","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche Ltd.","doi-asserted-by":"crossref","award":["AWD0002623"],"award-info":[{"award-number":["AWD0002623"]}],"id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100014566","name":"Celiac Disease Foundation","doi-asserted-by":"crossref","award":["na"],"award-info":[{"award-number":["na"]}],"id":[{"id":"10.13039\/501100014566","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001021","name":"Damon Runyon Cancer Research Foundation","doi-asserted-by":"publisher","award":["DRG-2316-18"],"award-info":[{"award-number":["DRG-2316-18"]}],"id":[{"id":"10.13039\/100001021","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,9,23]]},"abstract":"<jats:p>\n                    Murine and human immune systems differ significantly, particularly within the myeloid lineage. Humanized mice, generated by transplanting human hematopoietic stem, progenitor cells into genetically modified mice, are invaluable to study human immune development and function in vivo. However, a major limitation of current models is suboptimal myelopoiesis, particularly lack of functional human neutrophils, hampering the modeling of human immune responses and chronic diseases. Here, we describe a humanized mouse model, named MaGIC for genes replaced, in the\n                    <jats:italic toggle=\"yes\">C57Bl\/6 N<\/jats:italic>\n                    strain, which improves human myelopoiesis and enables development of functional human neutrophils. In MaGIC mice, human cytokines M-CSF\/CSF1(M), GM-CSF\/CSF2(G) and IL-6(I) are knocked-in replacing mouse genes and murine\n                    <jats:italic toggle=\"yes\">IL2rg and Rag1<\/jats:italic>\n                    (a) are deleted. Human THPO in these mice supports human hematopoiesis. More importantly, insertion of human CD47 (C) under the control of endogenous mouse CD47 promoter enables xenotransplantation and human neutrophil development. MaGIC mice support all human neutrophil subsets found in human bone marrow and blood, a major improvement. This is achieved by creating a niche postirradiation for human granulocyte\u2013macrophage progenitors via reduced murine CD47 and physiological levels of human CD47. These mice also have mature human monocytes, tissue macrophages, alveolar macrophages, dendritic cells, and NK cells, enabled by humanized M-CSF and GM-CSF. Human neutrophils in MaGIC mice are fully functional in chemotaxis, phagocytosis, reactive oxygen species production, and neutrophil extracellular trap formation in response to inflammation. MaGIC mice address critical gaps in current models and enable incisive translational research on human neutrophils, advancing studies in infectious, autoimmune, and inflammatory diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2426546122","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T17:55:08Z","timestamp":1758045308000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Humanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow"],"prefix":"10.1073","volume":"122","author":[{"given":"Esen","family":"Sefik","sequence":"first","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Philbrick","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Endocrinology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengrui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriti","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]},{"name":"Computational Biology & Biomedical Informatics Program, Yale University","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Van Lee","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7455-0609","authenticated-orcid":false,"given":"Johannes","family":"Sam","sequence":"additional","affiliation":[{"name":"Roche Innovation Center Zurich","place":["Schlieren, Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kutay","family":"Karatepe","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixin","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haris","family":"Mirza","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athreya","family":"Rangavajhula","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrine","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0111-2973","authenticated-orcid":false,"given":"Neha","family":"Arun","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Babu","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Eynon","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Chiorazzi","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8833-2514","authenticated-orcid":false,"given":"Liang","family":"Shan","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine in St.","place":["Louis, St. Louis"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Halene","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine","place":["New Haven"]},{"name":"Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8545-0451","authenticated-orcid":false,"given":"Hongbo R.","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Rongvaux","sequence":"additional","affiliation":[{"name":"Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center","place":["Seattle"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3035-071X","authenticated-orcid":false,"given":"Yuval","family":"Kluger","sequence":"additional","affiliation":[{"name":"Computational Biology & Biomedical Informatics Program, Yale University","place":["New Haven"]},{"name":"Department of Pathology, Yale School of Medicine","place":["New Haven"]},{"name":"Program in Applied Mathematics, Yale University","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4461-0778","authenticated-orcid":false,"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale School of Medicine","place":["New Haven"]},{"name":"HHMI, Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2016.12.006"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.2731"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0141-8"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1905054116"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20181468"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3399"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-01-259028"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2921"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.136.3.707"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12337"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2010.07659.x"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.9.5472"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00508"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203022"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1180"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.8.3446-3447.1992"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V46.6.913.913"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00738.2001"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.24.9233"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-445619"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2019-000473"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0736-z"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2009.06.017"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601807103"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-082523-124415"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2121077119"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-006921"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1019682108"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2858"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-326926"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-04-709584"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403222"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4202"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132557"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M112.025288"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1286-4"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V118.21.4008.4008"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-06-506949"},{"key":"e_1_3_4_39_2","unstructured":"E. Sefik Data from \u201cHumanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow.\u201d Gene Expression Omnibus (GEO). https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE303007. Deposited 18 July 2025."},{"key":"e_1_3_4_40_2","unstructured":"The Tabula Sapiens Consortium \u201cThe Tabula Sapiens: A multiple-organ single-cell transcriptomics atlas of humans\u201d Tabula Sapiens-Bone_Marrow. https:\/\/cellxgene.cziscience.com\/e\/4f1555bc-4664-46c3-a606-78d34dd10d92.cxg\/. Accessed 10 November 2023."},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl5197"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.11.026"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4091"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.03.005"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6581-6_2"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.046"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.06.001"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abe2485"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-06-585299"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-021-01155-4"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914351107"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003561"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-018-4772-0"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2426546122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T17:55:34Z","timestamp":1758045334000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2426546122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,16]]},"references-count":54,"journal-issue":{"issue":"38","published-print":{"date-parts":[[2025,9,23]]}},"alternative-id":["10.1073\/pnas.2426546122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2426546122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,16]]},"assertion":[{"value":"2024-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2426546122"}}