{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:50:09Z","timestamp":1783648209770,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pituitary neuroendocrine tumours (PitNETs) are common intracranial tumours that are highly heterogeneous with unpredictable growth patterns. The driver genes and mechanisms that are crucial for tumour progression in somatotroph PitNETs are poorly understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we performed integrative spatial transcriptomics (ST) and single\u2010cell RNA sequencing (scRNA\u2010seq) analysis on somatotroph tumours and normal pituitary samples to comprehensively characterize the differences in cellular characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>By analyzing combined copy number variations (CNVs), tumour tissues were divided into two regions, which included the CNV<jats:sub>high<\/jats:sub> and CNV<jats:sub>low<\/jats:sub> areas. The protumour genes DLK1 and RCN1 were highly expressed in the CNV<jats:sub>high<\/jats:sub> area, which might be related to tumour progression and could be targeted for precision therapy. We also found that the transforming growth factor beta signalling pathway participated in tumour progression and identified heterogeneity in the expression profiles of key genes. We assessed the intertumoral and intratumoral heterogeneity in somatotroph PitNETs and emphasized the importance of individualized treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In summary, we visualized the cellular distribution and transcriptional differences in normal pituitary and somatotroph PitNETs by ST and scRNA\u2010seq for the first time. This study provides a strong theoretical foundation to comprehensively understand the crucial mechanisms involved in tumour progression and develop new strategies to treat somatotroph PitNETs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The first\u2010ever visualization of cellular distributions in normal and tumor pituitary tissues.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The inter\u2010 and intra\u2010tumoral transcriptomic heterogeneity of somatotroph PitNETs was comprehensively revealed.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Identification of potential protumor factors and critical signaling pathways, opening new avenues for therapeutic intervention.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.70090","type":"journal-article","created":{"date-parts":[[2024,11,16]],"date-time":"2024-11-16T04:43:52Z","timestamp":1731732232000},"source":"Crossref","is-referenced-by-count":5,"title":["Comprehensive mapping of somatotroph pituitary neuroendocrine tumour heterogeneity using spatial and single\u2010cell transcriptomics"],"prefix":"10.1002","volume":"14","author":[{"given":"Jialin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Beijing Neurosurgical Institute Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Beijing Neurosurgical Institute Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital Affiliated to Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Annoroad Gene Technology (Beijing) Co., Ltd Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Tong","sequence":"additional","affiliation":[{"name":"Annoroad Gene Technology (Beijing) Co., Ltd Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehao","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Beijing Neurosurgical Institute Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Beijing Neurosurgical Institute Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxiaofeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Beijing Neurosurgical Institute Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Beijing Neurosurgical Institute Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, 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 Cell Biology, Beijing Neurosurgical Institute Capital Medical University Beijing China"},{"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":"Department of Cell Biology, Beijing Neurosurgical Institute Capital Medical University Beijing China"},{"name":"Department of Neurosurgery Beijing Tiantan Hospital Affiliated to Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6029-8521","authenticated-orcid":false,"given":"Weiyan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Beijing Neurosurgical Institute Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Beijing Tiantan Hospital Affiliated to Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI138540"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00736-5"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000533692"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-04272-1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0071-6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2010-0002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(22)00244-3"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.100934"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-023-00831-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.68436"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111223"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-21-1183"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01267-3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab102"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-022-02126-5"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-40271-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adf5464"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adh9069"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00962-8"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29366-6"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-2682"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-0747"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04724-5"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-021-00146-0"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnac010"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19012-4"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290264"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.09.129"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101230"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-020-00377-w"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3171\/2022.6.JNS22319"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1429"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26091-4"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.03.016"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11081156"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.03.007"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-023-02089-1"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-19-0327"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15133375"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2016.114"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-0790"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-21-0208"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209219"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2021.01.014"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0658-5"},{"issue":"3","key":"e_1_2_9_48_1","article-title":"Dlk1 promotes lung cancer cell invasion through upregulation of mmp9 expression depending on notch signalling","volume":"9","author":"Zhou Y","year":"2014","journal-title":"PLoS One"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11102-020-01091-7"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12022-022-09703-7"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3192"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.11.014"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ctm2.70090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T12:54:48Z","timestamp":1739278488000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ctm2.70090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":55,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/ctm2.70090"],"URL":"https:\/\/doi.org\/10.1002\/ctm2.70090","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11]]},"article-number":"e70090"}}