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This infiltration poses a significant surgical risk due to potential damage to vital nerves and arteries. However, the mechanisms underlying bone invasion caused by PitNETs remain elusive, and effective interventions for PitNET-induced bone invasion are lacking in clinical practice.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In this study, we performed single-cell (<jats:italic>n<\/jats:italic>\u2009=\u200987,287) RNA sequencing on 10 cases of bone-invasive PitNETs and 5 cases of non-bone-invasion PitNETs (Non-BI PitNETs). We identified various cell types and determined their interactions through cell-cell communication analysis, which was further validated experimentally.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We identified a novel TNF-\u03b1<jats:sup>+<\/jats:sup> TAM macrophage subset. BI PitNETs showed increased IL-34 secretion, impacting TNF-\u03b1<jats:sup>+<\/jats:sup> TAMs via the IL34\/CSF1R axis, leading to TNF-\u03b1 production. TNF-\u03b1<jats:sup>+<\/jats:sup> TAMs, in turn, communicate with <jats:italic>CD14<\/jats:italic>\n              <jats:sup>+<\/jats:sup> monocytes to promote their differentiation into osteoclasts and leading to bone invasion. In addition, we defined a gene signature for TNF-\u03b1<jats:sup>+<\/jats:sup> TAM to guide the clinical prognosis prediction of BI PitNETs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Our study elucidates the tumor microenvironment changes in bone invasion and identifies the critical role of TNF-\u03b1<jats:sup>+<\/jats:sup> TAMs in promoting bone invasion of PitNETs, laying a foundation for developing new molecular markers or therapeutic agents targeting BI PitNETs.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13046-025-03296-9","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T02:28:55Z","timestamp":1737944935000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Single-cell transcriptomics identify a novel macrophage population associated with bone invasion in pituitary neuroendocrine tumors"],"prefix":"10.1186","volume":"44","author":[{"given":"Xinzhi","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueshuai","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibo","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicheng","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuzhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazhuo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"issue":"12 Suppl 2","key":"3296_CR1","doi-asserted-by":"publisher","first-page":"iii1","DOI":"10.1093\/neuonc\/noab200","volume":"23","author":"QT Ostrom","year":"2021","unstructured":"Ostrom QT, Cioffi G, Waite K, Kruchko C, Barnholtz-Sloan JS. 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