{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T19:02:29Z","timestamp":1771786949702,"version":"3.50.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Intracranial germ cell tumors (iGCTs) are rare, histologically classified as extragonadal germ cell tumors, and predominantly affect children and adolescents. These tumors are commonly found in the midline of the brain, with a notable male predominance and varying geographic incidences. The origins of iGCTs have been debated, particularly whether they arise from abnormal migration of primordial germ cells (PGCs) or transformed embryonic stem cells (ESCs). In this study, we hypothesize the potential presence of PGC-like cells in the pituitary gland, and these cells may differentiate into iGCTs during the complex and frequent regulation of the hypothalamic-pituitary\u2013gonadal axis (HPGA).We analyzed the expression of four germ cell markers\u2014MVH, OCT4, C-kit, and PLZF\u2014using immunohistochemistry, Western blotting, and real-time quantitative PCR in human pituitary tissues, pituitary tumors, and pituitary germ cell tumors. Our findings indicate significant expression of these markers in pituitary tissues, with the highest levels found in pituitary germ cell tumors. These results support the existence of PGC-like cells that within the normal pituitary gland. This study provides new insights into the cellular origins of iGCTs and suggests further investigation into the regulatory mechanisms that may lead to tumorigenesis.<\/jats:p>","DOI":"10.1038\/s41598-026-38060-2","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T12:37:54Z","timestamp":1770122274000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Primordial germ cell-like cells residing in the pituitary may serve as the origin of intracranial germ cell tumors"],"prefix":"10.1038","volume":"16","author":[{"given":"Yi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengyang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jifang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhang","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daishu","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,3]]},"reference":[{"key":"38060_CR1","doi-asserted-by":"crossref","unstructured":"D.N. Louis, A. Perry, P. Wesseling, D.J. Brat, I.A. Cree, D. Figarella-Branger, C. Hawkins, H.K. Ng, S.M. Pfister, G. Reifenberger, R. Soffietti, A. von Deimling, D.W. Ellison, The 2021 WHO Classification of Tumors of the Central Nervous System: a summary, Neuro-oncology, 23 (2021) 1231\u20131251.","DOI":"10.1093\/neuonc\/noab106"},{"key":"38060_CR2","doi-asserted-by":"publisher","first-page":"155","DOI":"10.3171\/jns.1985.63.2.0155","volume":"63","author":"MT Jennings","year":"1985","unstructured":"Jennings, M. T., Gelman, R. & Hochberg, F. Intracranial germ-cell tumors: Natural history and pathogenesis. J Neurosurg 63, 155\u2013167 (1985).","journal-title":"J Neurosurg"},{"key":"38060_CR3","doi-asserted-by":"crossref","unstructured":"H. Gittleman, G. Cioffi, T. Vecchione-Koval, Q.T. Ostrom, C. Kruchko, D.S. Osorio, J.L. Finlay, J.S. Barnholtz-Sloan, Descriptive epidemiology of germ cell tumors of the central nervous system diagnosed in the United States from 2006 to 2015, Journal of neuro-oncology, 143 (2019) 251-260.","DOI":"10.1007\/s11060-019-03173-4"},{"key":"38060_CR4","doi-asserted-by":"publisher","first-page":"e472","DOI":"10.1016\/j.wneu.2018.10.082","volume":"122","author":"Y Zhang","year":"2019","unstructured":"Zhang, Y. et al. Delays in diagnosis of pediatric histologically confirmed sellar germ cell tumors in China: A retrospective risk factor analysis. World Neurosurg. 122, e472\u2013e479 (2019).","journal-title":"World Neurosurg."},{"key":"38060_CR5","doi-asserted-by":"publisher","first-page":"16","DOI":"10.14791\/btrt.2013.1.1.16","volume":"1","author":"KW Jung","year":"2013","unstructured":"Jung, K. W., Ha, J., Lee, S. H., Won, Y. J. & Yoo, H. An updated nationwide epidemiology of primary brain tumors in republic of Korea. Brain Tumor Res. Treat. 1, 16\u201323 (2013).","journal-title":"Brain Tumor Res. Treat."},{"key":"38060_CR6","first-page":"e470","volume":"16","author":"MJ Murray","year":"2015","unstructured":"Murray, M. J. et al. Consensus on the management of intracranial germ-cell tumours, The Lancet. Oncology 16, e470\u2013e477 (2015).","journal-title":"Oncology"},{"key":"38060_CR7","doi-asserted-by":"publisher","first-page":"333","DOI":"10.3332\/ecancer.2013.333","volume":"7","author":"MJ Murray","year":"2013","unstructured":"Murray, M. J., Horan, G., Lowis, S. & Nicholson, J. C. Highlights from the third international central nervous system germ cell tumour symposium: Laying the foundations for future consensus. Ecancermedicalscience 7, 333 (2013).","journal-title":"Ecancermedicalscience"},{"key":"38060_CR8","doi-asserted-by":"publisher","first-page":"4290","DOI":"10.1002\/cncr.27403","volume":"118","author":"RS Arora","year":"2012","unstructured":"Arora, R. S., Alston, R. D., Eden, T. O., Geraci, M. & Birch, J. M. Comparative incidence patterns and trends of gonadal and extragonadal germ cell tumors in England, 1979 to 2003. Cancer 118, 4290\u20134297 (2012).","journal-title":"Cancer"},{"key":"38060_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.604519","volume":"11","author":"E Laporte","year":"2020","unstructured":"Laporte, E., Vennekens, A. & Vankelecom, H. Pituitary remodeling throughout life: Are resident stem cells involved?. Front. Endocrinol. 11, 604519 (2020).","journal-title":"Front. Endocrinol."},{"key":"38060_CR10","doi-asserted-by":"publisher","first-page":"5275","DOI":"10.1038\/s41467-020-19012-4","volume":"11","author":"S Zhang","year":"2020","unstructured":"Zhang, S. et al. Single-cell transcriptomics identifies divergent developmental lineage trajectories during human pituitary development. Nat. Commun. 11, 5275 (2020).","journal-title":"Nat. Commun."},{"key":"38060_CR11","doi-asserted-by":"publisher","first-page":"17259","DOI":"10.1038\/s41598-022-22137-9","volume":"12","author":"M Amirian","year":"2022","unstructured":"Amirian, M., Azizi, H., Hashemi Karoii, D. & Skutella, T. VASA protein and gene expression analysis of human non-obstructive azoospermia and normal by immunohistochemistry, immunocytochemistry, and bioinformatics analysis. Sci. Rep. 12, 17259 (2022).","journal-title":"Sci. Rep."},{"key":"38060_CR12","doi-asserted-by":"publisher","first-page":"5677","DOI":"10.3390\/cimb45070358","volume":"45","author":"VE Adashev","year":"2023","unstructured":"Adashev, V. E., Kotov, A. A. & Olenina, L. V. RNA helicase vasa as a multifunctional conservative regulator of gametogenesis in eukaryotes. Curr. Issues Mol. Biol. 45, 5677\u20135705 (2023).","journal-title":"Curr. Issues Mol. Biol."},{"key":"38060_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.610665","volume":"11","author":"VE Adashev","year":"2020","unstructured":"Adashev, V. E. et al. Stellate genes and the piRNA pathway in speciation and reproductive isolation of drosophila melanogaster. Front. Genet. 11, 610665 (2020).","journal-title":"Front. Genet."},{"key":"38060_CR14","doi-asserted-by":"crossref","unstructured":"W. Li, P. Zhang, X. Wu, X. Zhu, H. Xu, A Novel Dynamic Expression of vasa in Male Germ Cells during Spermatogenesis in the Chinese Soft-Shell Turtle (Pelidiscus sinensis), Journal of experimental zoology. Part B, Molecular and developmental evolution, 328 (2017) 230-239.","DOI":"10.1002\/jez.b.22728"},{"key":"38060_CR15","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1111\/apm.12028","volume":"121","author":"X Li","year":"2013","unstructured":"Li, X. et al. Enrichment of Oct3\/4-positive cells from a human bronchial epithelial cell line. APMIS\u202f: Acta Pathologica, Microbiologica, Et Immunologica Scandinavica 121, 612\u2013625 (2013).","journal-title":"APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica"},{"key":"38060_CR16","first-page":"149","volume":"15","author":"KW Ngan","year":"2008","unstructured":"Ngan, K. W. et al. Immunohistochemical expression of OCT4 in primary central nervous system germ cell tumours. J. Clin. Neurosci. Off. J. Neurosurg. Soc. Australasia 15, 149\u2013152 (2008).","journal-title":"J. Clin. Neurosci. Off. J. Neurosurg. Soc. Australasia"},{"key":"38060_CR17","doi-asserted-by":"publisher","first-page":"1169179","DOI":"10.3389\/fnins.2023.1169179","volume":"17","author":"Y Zhang","year":"2023","unstructured":"Zhang, Y. et al. OCT3\/4 is a potential immunohistochemical biomarker for diagnosis and prognosis of primary intracranial germ cell tumors: A systematic review and meta-analysis. Front. Neurosci. 17, 1169179 (2023).","journal-title":"Front. Neurosci."},{"key":"38060_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105263","volume":"106","author":"Y Luan","year":"2024","unstructured":"Luan, Y., So, W., Dong, R., Abazarikia, A. & Kim, S. Y. KIT in oocytes: A key factor for oocyte survival and reproductive lifespan. EBioMedicine 106, 105263 (2024).","journal-title":"EBioMedicine"},{"key":"38060_CR19","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1152\/physrev.00046.2011","volume":"92","author":"J Lennartsson","year":"2012","unstructured":"Lennartsson, J. & R\u00f6nnstrand, L. Stem cell factor receptor\/c-Kit: from basic science to clinical implications. Physiol. Rev. 92, 1619\u20131649 (2012).","journal-title":"Physiol. Rev."},{"key":"38060_CR20","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/ng1366","volume":"36","author":"FW Buaas","year":"2004","unstructured":"Buaas, F. W. et al. Plzf is required in adult male germ cells for stem cell self-renewal. Nat. Genet. 36, 647\u2013652 (2004).","journal-title":"Nat. Genet."},{"key":"38060_CR21","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.theriogenology.2023.12.015","volume":"215","author":"X Du","year":"2024","unstructured":"Du, X. et al. PLZF protein forms a complex with protein TET1 to target TCF7L2 in undifferentiated spermatogonia. Theriogenology 215, 321\u2013333 (2024).","journal-title":"Theriogenology"},{"key":"38060_CR22","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/0003-2697(85)90442-7","volume":"150","author":"PK Smith","year":"1985","unstructured":"Smith, P. K. et al. Measurement of protein using bicinchoninic acid. Anal. Biochem. 150, 76\u201385 (1985).","journal-title":"Anal. Biochem."},{"key":"38060_CR23","doi-asserted-by":"publisher","first-page":"4350","DOI":"10.1073\/pnas.76.9.4350","volume":"76","author":"H Towbin","year":"1979","unstructured":"Towbin, H., Staehelin, T. & Gordon, J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. U.S.A. 76, 4350\u20134354 (1979).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"38060_CR24","doi-asserted-by":"crossref","unstructured":"D.H. Castrillon, B.J. Quade, T.Y. Wang, C. Quigley, C.P. Crum, 2000 The human <i>VASA<\/i> gene is specifically expressed in the germ cell lineage, 97 9585\u20139590.","DOI":"10.1073\/pnas.160274797"},{"key":"38060_CR25","doi-asserted-by":"crossref","unstructured":"T. Garcia, M.C. Hofmann, Isolation of undifferentiated and early differentiating type A spermatogonia from Pou5f1-GFP reporter mice, Methods in molecular biology (Clifton, N.J.), 825 (2012) 31\u201344.","DOI":"10.1007\/978-1-61779-436-0_3"},{"key":"38060_CR26","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.ydbio.2014.10.020","volume":"397","author":"JT Busada","year":"2015","unstructured":"Busada, J. T. et al. Retinoic acid regulates Kit translation during spermatogonial differentiation in the mouse. Dev. Biol. 397, 140\u2013149 (2015).","journal-title":"Dev. Biol."},{"key":"38060_CR27","doi-asserted-by":"crossref","unstructured":"M. Sharma, A. Srivastava, H.E. Fairfield, D. Bergstrom, W.F. Flynn, R.E. Braun, Identification of EOMES-expressing spermatogonial stem cells and their regulation by PLZF, Elife, 8 (2019).","DOI":"10.7554\/eLife.43352"},{"key":"38060_CR28","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1111\/apm.1965.64.4.407","volume":"64","author":"G Teilum","year":"1965","unstructured":"Teilum, G. Classification of endodermal sinus tumour (mesoblatoma vitellinum) and so-called \u201cembryonal carcinoma\u201d of the ovary. Acta Pathol. Microbiol. Scand. 64, 407\u2013429 (1965).","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"38060_CR29","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s00401-017-1673-2","volume":"133","author":"S Fukushima","year":"2017","unstructured":"Fukushima, S. et al. Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas. Acta Neuropathol. 133, 445\u2013462 (2017).","journal-title":"Acta Neuropathol."},{"key":"38060_CR30","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3171\/jns.1999.90.2.0258","volume":"90","author":"K Sano","year":"1999","unstructured":"Sano, K. Pathogenesis of intracranial germ cell tumors reconsidered. J. Neurosurg. 90, 258\u2013264 (1999).","journal-title":"J. Neurosurg."},{"key":"38060_CR31","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1002\/path.4098","volume":"229","author":"C Tan","year":"2013","unstructured":"Tan, C. & Scotting, P. J. Stem cell research points the way to the cell of origin for intracranial germ cell tumours. J. Pathol. 229, 4\u201311 (2013).","journal-title":"J. Pathol."},{"key":"38060_CR32","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/978-3-319-16537-0_4","volume":"853","author":"B Manoranjan","year":"2015","unstructured":"Manoranjan, B., Garg, N., Bakhshinyan, D. & Singh, S. K. The role of stem cells in pediatric central nervous system malignancies. Adv. Exp. Med. Biol. 853, 49\u201368 (2015).","journal-title":"Adv. Exp. Med. Biol."},{"key":"38060_CR33","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/s41568-019-0178-9","volume":"19","author":"JW Oosterhuis","year":"2019","unstructured":"Oosterhuis, J. W. & Looijenga, L. H. J. Human germ cell tumours from a developmental perspective. Nat. Rev. Cancer 19, 522\u2013537 (2019).","journal-title":"Nat. Rev. Cancer"},{"key":"38060_CR34","first-page":"E367","volume":"311","author":"AM Vaca","year":"2016","unstructured":"Vaca, A. M. et al. The expansion of adult stem\/progenitor cells and their marker expression fluctuations are linked with pituitary plastic adaptation during gestation and lactancy, American journal of physiology. Endocrinol. Metabolism 311, E367-379 (2016).","journal-title":"Endocrinol. Metabolism"},{"key":"38060_CR35","doi-asserted-by":"publisher","DOI":"10.1111\/jne.13051","volume":"33","author":"CB Guido","year":"2021","unstructured":"Guido, C. B. et al. Changes of stem cell niche during experimental pituitary tumor development. J. Neuroendocrinol. 33, e13051 (2021).","journal-title":"J. Neuroendocrinol."},{"key":"38060_CR36","doi-asserted-by":"publisher","first-page":"45","DOI":"10.14791\/btrt.2024.0045","volume":"13","author":"E Lee","year":"2025","unstructured":"Lee, E. et al. Treatment outcomes and prognostic factors of intracranial germ cell tumors: A single institution retrospective study. Brain Tumor Res. Treat. 13, 45\u201352 (2025).","journal-title":"Brain Tumor Res. Treat."},{"key":"38060_CR37","doi-asserted-by":"crossref","unstructured":"J. Chernoff, The two-hit theory hits 50, Molecular Biology of the Cell, 32 (2021) rt1.","DOI":"10.1091\/mbc.E21-08-0407"},{"key":"38060_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.lmd.2025.100076","volume":"2","author":"C-C Zhang","year":"2025","unstructured":"Zhang, C.-C., Feng, H.-R., Zhu, J. & Hong, W.-F. Application of spatial and single-cell omics in tumor immunotherapy biomarkers. LabMed Discov. 2, 100076 (2025).","journal-title":"LabMed Discov."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38060-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38060-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38060-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T18:03:45Z","timestamp":1771783425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-38060-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,3]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["38060"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-38060-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,3]]},"assertion":[{"value":"9 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"7086"}}