{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:39:19Z","timestamp":1792604359068,"version":"4.5.0"},"reference-count":79,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Radioresistance severely compromises radiotherapy efficacy for lung adenocarcinoma (LUAD), yet the intrinsic heterogeneity of cellular radioresponses among isogenic tumor cells remains poorly characterized. Here, we integrated single\u2010cell RNA sequencing (scRNA\u2010seq) and single\u2010cell assay for transposase\u2010accessible chromatin with high\u2010throughput sequencing (scATAC\u2010seq) to dissect the transcriptional and regulatory landscape underlying heterogeneous radioresponses in single\u2010cell\u2010derived LUAD cells following 6\u00a0Gy \u03b3\u2010ray irradiation. We found that isogenic LUAD cells harbored intrinsic molecular determinants for divergent radiosensitivity and displayed heterogeneous radioresponsiveness upon irradiation. A radiation\u2010associated transcriptional cell state, coupled with DNA damage repair, apoptosis, and cell cycle regulation, emerged at 6\u00a0h post\u2010irradiation. Inhibition of lysine demethylase 4B (\n                    <jats:italic>KDM4<\/jats:italic>\n                    B) enhanced LUAD radiosensitivity by intensifying DNA damage, whereas reduced expression of cyclin\u00a0B1 (\n                    <jats:italic>CCNB1<\/jats:italic>\n                    ) and DNA topoisomerase\u00a0II\u03b1 (\n                    <jats:italic>TOP2A<\/jats:italic>\n                    ) potentially contributed to radiation\u2010triggered G2\/M arrest. Notably, the radiation\u2010associated regulatory cell state emerged earlier than radiation\u2010induced transcriptional cell state. RNA polymerase\u00a0II subunit\u00a0A (POLR2A) functioned as a core regulator in high\u2010responsive LUAD cells. Based on these findings, we proposed a hypothesis for the radiosensitization of LUAD cells. Collectively, this study provides multilayer mechanistic insights into LUAD radioresponse heterogeneity and yields actionable molecular candidates for developing improved radiosensitization strategies to advance precise radiotherapy for LUAD.\n                  <\/jats:p>","DOI":"10.1002\/mco2.71071","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:01:39Z","timestamp":1792602099000},"source":"Crossref","is-referenced-by-count":0,"title":["Dissecting the Radioresponse Heterogeneity of Lung Adenocarcinoma Cells From the Perspective of Transcriptional and Regulatory Landscape"],"prefix":"10.1002","volume":"7","author":[{"given":"Huan","family":"Tao","sequence":"first","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Li","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leixin","family":"Ge","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyue","family":"Ma","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhui","family":"Ge","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjiang","family":"Fu","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longteng","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Statistical Science Center for Bioinformatics School of Life Sciences Peking University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junting","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Bai","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Bo","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hebing","family":"Chen","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1608986"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00648-7"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-018-0167-4"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-023-01801-2"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00312-3"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1133899"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1118\/1.4875686"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-8140(90)90115-D"},{"issue":"2","key":"e_1_2_12_10_1","first-page":"513","article-title":"A Heterogeneous Cellular Response to Ionizing Radiation Revealed by Single Cell Transcriptome Sequencing","volume":"11","author":"Gao Y.","year":"2021","journal-title":"Americal Journal of Cancer Research"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26041433"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-023-10260-4"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13246-018-0684-1"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0360-3016(00)01524-8"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6826"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0969-x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07493-y"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adh2602"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01577-7"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12078"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-021-01105-2"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06342-8"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbaa127"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/1559325817690638"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-021-01282-5"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17324-z"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25643-y"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2022.07.004"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:CANC.0000031762.91306.b4"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20047-w"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-00803-5"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_12_33_1","first-page":"2122","article-title":"A Step\u2010by\u2010Step Workflow for Low\u2010Level Analysis of Single\u2010Cell RNA\u2010seq Data With Bioconductor","volume":"5","author":"Lun A. T.","year":"2016","journal-title":"F1000Res"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2013.06.007"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2006.07.007"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206677"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21145-z"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-021-00200-0"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.16005"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.491514"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604381"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-025-01053-7"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.12.002"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-025-01607-3"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.2741\/A772"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1410308"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1663-x"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-014-0032-x"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.202209125"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.045"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0414-6"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21246-9"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104745"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2007.03.009"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/1642852"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.52319"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1177\/1559325819891008"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4401"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.09.001"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553002.2019.1665216"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0367-1"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv145"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2004.tb02195.x"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz024"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00041"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206682"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.11.003"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S290438"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-15-0189"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.723"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.30"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0007-6"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12593"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3960"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15058"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.06.034"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-31702-9"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-023-02916-x"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"}],"container-title":["MedComm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.71071","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mco2.71071","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.71071","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:01:40Z","timestamp":1792602100000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mco2.71071"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,21]]},"references-count":79,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1002\/mco2.71071"],"URL":"https:\/\/doi.org\/10.1002\/mco2.71071","archive":["Portico"],"relation":{},"ISSN":["2688-2663","2688-2663"],"issn-type":[{"value":"2688-2663","type":"print"},{"value":"2688-2663","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,21]]},"article-number":"e71071"}}