{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:16:36Z","timestamp":1784733396360,"version":"3.55.0"},"reference-count":68,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82072804"],"award-info":[{"award-number":["82072804"]}],"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":["82071558"],"award-info":[{"award-number":["82071558"]}],"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":["82071559"],"award-info":[{"award-number":["82071559"]}],"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":["82141109"],"award-info":[{"award-number":["82141109"]}],"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":["81672495"],"award-info":[{"award-number":["81672495"]}],"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":["82203174"],"award-info":[{"award-number":["82203174"]}],"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":["82103028"],"award-info":[{"award-number":["82103028"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["Z220012"],"award-info":[{"award-number":["Z220012"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7232015"],"award-info":[{"award-number":["7232015"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The three\u2010dimensional (3D) genome architecture plays a critical role inregulating gene expression. However, the specific alterations in thisarchitecture within somatotroph tumors and their implications for gene expression remain largely unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We employed Hi\u2010C and RNA\u2010seq analyses to compare the 3D genomic structures of somatotroph tumors with normal pituitary tissue. This comprehensive approachenabled the characterization of A\/B compartments, topologically associateddomains (TADs), and chromatin loops, integrating these with gene expression patterns.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed a decrease in both the frequency of chromosomal interactions andthe size of TADs in tumor tissue compared to normal tissue. Conversely, the number of TADs and chromatin loops was found to be increased in tumors. Integrated analysis of Hi\u2010C and RNA\u2010seq data demonstrated that changes inhigher\u2010order chromat in structure were associated with alterations in gene expression. Specifically, genes in A compartments showed higher density and increased expression relative to those in B compartments. Moreover, the weakand enhanced insulation boundaries were identified, and the associated genes were enriched in the Wnt\/\u03b2\u2010Catenin signaling pathway. We identified the gainedand lost loops in tumor and integrated these differences with transcriptional changes to examine the functional relevance of the identified loops. Notably, we observed an enhanced insulation boundary and a greater number of loops in the TCF7L2 gene region within tumors, which was accompanied by an upregulation of TCF7L2 expression. Subsequently, TCF7L2 expression was confirmed through qRT\u2010PCR, and upregulated TCF7L2 prompted cell proliferation and growth hormone (GH) secretion in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results provide comprehensive 3D chromatin architecture maps of somatotroph tumors and offer a valuable resource for furthering the understanding of the underlying biology and mechanisms of gene expression regulation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1682","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T04:44:30Z","timestamp":1716266670000},"source":"Crossref","is-referenced-by-count":3,"title":["Three\u2010dimensional chromatin landscapes in somatotroph tumour"],"prefix":"10.1002","volume":"14","author":[{"given":"Jing","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital affiliated to Capital Medical University  Beijing China"},{"name":"Beijing Neurosurgical Institute Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital affiliated to Capital Medical University  Beijing China"},{"name":"Beijing Neurosurgical Institute Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital affiliated to Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Tong","sequence":"additional","affiliation":[{"name":"Annoroad Gene Technology Co., Ltd  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital affiliated to Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazhuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Neurosurgical Institute Capital Medical University  Beijing China"},{"name":"Beijing Institute for Brain Disorders Brain Tumor Center  Beijing China"},{"name":"China National Clinical Research Center for Neurological Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyan","family":"Xie","sequence":"additional","affiliation":[{"name":"Beijing Neurosurgical Institute Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0256-1261","authenticated-orcid":false,"given":"Chuzhong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital affiliated to Capital Medical University  Beijing China"},{"name":"Beijing Neurosurgical Institute Capital Medical University  Beijing China"},{"name":"Beijing Institute for Brain Disorders Brain Tumor Center  Beijing China"},{"name":"China National Clinical Research Center for Neurological Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12753"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010018\u20100060\u20108"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2016.112"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14222"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11082"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1181369"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.055"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.04.004"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010018\u20100007\u20100"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad9024"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.201517.115"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010019\u20100128\u20100"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.021"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.10.023"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.288324.116"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou223"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1810772"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.19699"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102265.2009.03667.x"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006\u20101668"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010019\u20100071\u20106"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541\u20107786.mcr\u201019\u20100434"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102\u2010017\u20100789\u20107"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9010030"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2022.02.002"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC\u201013\u20100005"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10883"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010020\u20101259\u20107"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010019\u20101315\u20108"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010015\u20100831\u2010x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1923"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.220640.117"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.07.009"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3317"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010014\u20100550\u20108"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2016.07.002"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa073"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046\u2010022\u201002245\u20100"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2006.04.007"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.092759.109"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010015\u20100768\u20100"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020\u2010018\u20101677\u20102"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.018"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.05.004"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164594"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.014"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.72982"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.02.040"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00290"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw1668"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051110"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3816\/CCC.2011.n.004"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7310078"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2016.03.008"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2013.04.034"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201005\u20100884"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1906484116"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.23"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.022"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201012079\u20108"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2011.639361"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2016.00054"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2016.00013"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.016"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010019\u20100466\u2010z"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19800"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010018\u20100367\u20106"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.1682","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T04:22:52Z","timestamp":1716956572000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.1682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":68,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/ctm2.1682"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.1682","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"article-number":"e1682"}}