{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T08:04:22Z","timestamp":1780473862219,"version":"3.54.1"},"reference-count":69,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471754"],"award-info":[{"award-number":["82471754"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771337"],"award-info":[{"award-number":["81771337"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201545"],"award-info":[{"award-number":["82201545"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010029","name":"Taishan Scholar Foundation of Shandong Province","doi-asserted-by":"publisher","award":["tsqn202312392"],"award-info":[{"award-number":["tsqn202312392"]}],"id":[{"id":"10.13039\/501100010029","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014103","name":"Key Technology Research and Development Program of Shandong Province","doi-asserted-by":"publisher","award":["2024CXPT091"],"award-info":[{"award-number":["2024CXPT091"]}],"id":[{"id":"10.13039\/100014103","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Perinatal hypoxia\u2013ischemia is a leading cause of preterm white matter injury (PWMI), yet mechanisms underlying oligodendrocyte precursor cells (OPCs) dysfunction remain poorly understood. Here, we identify endothelial\u2010derived Netrin\u20104 (\n                    <jats:italic>Ntn4<\/jats:italic>\n                    ) as a critical regulator of OPCs proliferation and differentiation in PWMI. Developmental analysis revealed that Netrin\u20104, predominantly expressed in cerebrovascular endothelial cells (ECs), peaks during postnatal myelination and correlates with OPCs marker PDGFR\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    . Conditional endothelial deletion of\n                    <jats:italic>Ntn4<\/jats:italic>\n                    in mice impaired spatial memory, induced anxiety\u2010like behavior, and reduced mature oligodendrocytes, accompanied by disrupted myelin ultrastructure. In a PWMI model, endothelial\n                    <jats:italic>Ntn4<\/jats:italic>\n                    knockout exacerbated myelination deficits and suppressed OPCs proliferation, while inducible deletion at later stages enhanced OPCs differentiation. Mechanistically, Netrin\u20104\u2010overexpressing ECs elevated ET\u20101 secretion, which promoted OPCs proliferation but inhibited differentiation via ET\u20101 receptor EDNRB. Our findings reveal that endothelial Netrin\u20104 is a dual regulator of OPCs dynamics in PWMI, driving proliferation via ET\u20101 while impairing differentiation. Targeting the Netrin\u20104\/ET\u20101 axis restores OPCs maturation, offering a potential strategy to mitigate myelination deficits in PWMI.\n                  <\/jats:p>","DOI":"10.1111\/bpa.70067","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:59:41Z","timestamp":1768456781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Endothelial Netrin\u20104 regulates oligodendrocyte precursor cell proliferation and differentiation via\n                    <scp>ET<\/scp>\n                    \u20101 signaling in preterm white matter injury"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0430-3124","authenticated-orcid":false,"given":"Fuxing","family":"Dong","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology Xuzhou Medical University  Xuzhou Jiangsu Province China"},{"name":"Public Experimental Research Center Xuzhou Medical University  Xuzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixing","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology Xuzhou Medical University  Xuzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology Xuzhou Medical University  Xuzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology Xuzhou Medical University  Xuzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology Xuzhou Medical University  Xuzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Liu","sequence":"additional","affiliation":[{"name":"National Demonstration Center for Experimental Basic Medical Science Education Xuzhou Medical University  Xuzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy Xuzhou Medical University  Xuzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5418-3354","authenticated-orcid":false,"given":"Chao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Neurology, Yantai Yuhuangding Hospital Qingdao University  Yantai Shandong Province China"},{"name":"Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital Qingdao University  Yantai Shandong Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqin","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology Xuzhou Medical University  Xuzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00354-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.7189\/jogh.14.04109"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1718-6"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000254729.27386.05"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2015.11.002"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20530"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70294-1"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24132"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.20107"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A1399"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-009-1389-0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22139"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.07.017"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2480"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-020-00583-7"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.052"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3213-07.2008"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21359"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad3839"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0369-4"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.10.032"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22658"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0035-09.2009"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2019.11.013"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1944-11.2011"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02157-4"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900866RR"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13515"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-022-01279-4"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.289371"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.21424"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2004.07.009"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9061137"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.001503"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0822-09.2009"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.10.002"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16028-8"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.193712"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155280"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00748-y"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3466.2002.tb00082.x"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.12105"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1163400"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00032-3"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrdd.10007"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410090206"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1592-15.2015"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-025-04267-9"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(00)00369-5"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20474"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.2.221"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2008.128"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23746"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2006.11.002"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2013.03.015"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813286106"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn917"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.136"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-019-0176-3"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-6997(25)06809-7"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2013.07.005"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5652-07.2008"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.9887"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.11.015"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.11.002"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12347"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-020-01085-3"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-031-87919-7_1"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24238"}],"container-title":["Brain Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.70067","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bpa.70067","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bpa.70067","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:35:00Z","timestamp":1780472100000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bpa.70067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":69,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/bpa.70067"],"URL":"https:\/\/doi.org\/10.1111\/bpa.70067","archive":["Portico"],"relation":{},"ISSN":["1015-6305","1750-3639"],"issn-type":[{"value":"1015-6305","type":"print"},{"value":"1750-3639","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]},"assertion":[{"value":"2025-10-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70067"}}