{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:14:57Z","timestamp":1781108097344,"version":"3.54.1"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"41","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Key Research and Development Project","award":["2023YFA1800100"],"award-info":[{"award-number":["2023YFA1800100"]}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270873 32470862"],"award-info":[{"award-number":["32270873 32470862"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chongqing Population and Health Special Funding of China","award":["CSTB2023TIAD-KPX0056"],"award-info":[{"award-number":["CSTB2023TIAD-KPX0056"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,10,14]]},"abstract":"<jats:p>\n                    As critical executors of the immune system, neutrophils provide an immediate inflammatory response for the clearance of debris and microbes, which is essential for the protection of health. Developmentally, neutrophils and macrophages share common progenitors, whose fate is tightly controlled by transcriptional programs. Dysregulation of these programs causes severe hematological disorders, including neutropenia, neutrophilia, leukemia, and inflammatory disorders. However, the mechanisms underlying the generation of neutrophils through these programs are poorly understood. Here, we revealed that Ikzf1 and Myb were enriched in neutrophils. Overactivation of Ikzf1 promoted neutrophil generation while suppressing macrophage emergence. Conversely, the simultaneous loss of Ikzf1 and Myb, but not the individual mutations, drastically impaired neutrophil production and enlarged the macrophage pool in both zebrafish and mice. Mechanistically, Ikzf1 and Myb formed a complex that targeted\n                    <jats:italic toggle=\"yes\">irf8<\/jats:italic>\n                    and induced the expression of a long noncoding RNA (lncRNA),\n                    <jats:italic toggle=\"yes\">irf8-2<\/jats:italic>\n                    , through a regulatory element. LncRNA\n                    <jats:italic toggle=\"yes\">irf8-2<\/jats:italic>\n                    biased neutrophil commitment by modulating\n                    <jats:italic toggle=\"yes\">irf8<\/jats:italic>\n                    dosage via Zfp36l1. The deletion of\n                    <jats:italic toggle=\"yes\">irf8-2<\/jats:italic>\n                    resulted in defective neutrophil development and enhanced macrophage production. However, a partial ratio of neutrophils and macrophages was restored when Ikzf1, Myb, and Irf8 were all compromised. Overall, our study reveals that Ikzf1 and Myb cooperatively bias neutrophil development against Irf8 via the lncRNA\n                    <jats:italic toggle=\"yes\">irf8<\/jats:italic>\n                    -2 and Zfp36l. This study provides previously uncharacterized insights into the conserved molecular balance between neutrophil and macrophage development during myelopoiesis, with potential implications for understanding and treating myeloid disorders.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2502741122","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:21:19Z","timestamp":1759940479000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of an lncRNA\n                    <i>irf8<\/i>\n                    by the Ikzf1\/Myb complex drives neutrophil development"],"prefix":"10.1073","volume":"122","author":[{"given":"Yuepeng","family":"He","sequence":"first","affiliation":[{"name":"Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences","place":["Chongqing, People\u2019s Republic of 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Reproduction and Development, Ministry of Education, Southwest University","place":["Chongqing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangyong","family":"He","sequence":"additional","affiliation":[{"name":"Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences","place":["Chongqing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengnan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University","place":["Chongqing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Laboratory of Developmental Biology, Department of Cell Biology and Genetics, Chongqing Medical University","place":["Chongqing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigang","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Laboratory of Developmental Biology, Department of Cell Biology and Genetics, Chongqing Medical University","place":["Chongqing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Hou","sequence":"additional","affiliation":[{"name":"Institute of Life Sciences, Laboratory of Developmental Biology, Department of Cell Biology and Genetics, Chongqing Medical University","place":["Chongqing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5318-8137","authenticated-orcid":false,"given":"Lingfei","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University","place":["Chongqing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Developmental Biology and Regenerative Medicine, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Southwest University","place":["Chongqing, People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6920-3311","authenticated-orcid":false,"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center of Stem Cells and Ageing, Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences","place":["Chongqing, People\u2019s Republic of 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Han , Microrna 449c mediates the generation of monocytic myeloid-derived suppressor cells by targeting STAT6. Mol. Cells 43, 793\u2013803 (2020).","journal-title":"Mol. Cells"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.10.021"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20200069"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.06.005"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30440-2"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90407-3"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00871-y"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.83342"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-162495"},{"key":"e_1_3_4_60_2","unstructured":"Y. He RNA-seq ATAC-seq and scRNA-seq data for \u201cRegulation of an lncRNA irf8 by the Ikzf1\/Myb complex drives neutrophil development.\u201d Gene Expression Omnibus. https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE306885. 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