{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:49:16Z","timestamp":1790790556576,"version":"4.1.0"},"reference-count":74,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000921","name":"European Cooperation in Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000921","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Testicular germ cell tumours (TGCTs) are amongst the most common malignancies in young men, and their incidence is increasing worldwide. Tissue heterogeneity hampers efforts to understand how TGCT precursors (termed germ cell neoplasia in situ; GCNIS) emerge and progress, restricting elucidation of new strategies for diagnosis and management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study reports the use of spatial transcriptomic analysis in TGCT tissue sections.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Over 90 regions of interest (ROIs) were identified in sections from four TGCT patients\u2019 samples, three with non\u2010seminoma, one seminoma. Transcripts in each ROI were sequenced and examined using the NanoString GeoMx spatial whole transcriptomics workflow, the values normalised and analysed using Degust RNA\u2010Seq and Ingenuity Pathway Analysis software.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The distribution and expression of functional markers in specific cell types was used to map individual tumours, GCNIS, and tumour\u2010adjacent regions. Significant heterogeneity in TGCTs and surrounding areas is documented between patients and across different regions in the same tumour. Immune cell\u2010related transcripts encoding macrophage, T cell, B cell, natural killer cell, dendritic cells and neutrophil subsets were identified as contributing substantially to tumour heterogeneity. Assessment of ROIs containing GCNIS and areas immediately adjacent from two individual non\u2010seminoma tumour samples identified the TGF\u03b2 family as contributing to upstream regulation of transcripts in both patients; known activin A target genes were differentially expressed between the GCNIS and microenvironment ROIs. In addition, two discrete tumour areas within the seminoma sample displayed distinct transcript profiles, one featuring higher levels of immune cell\u2010related transcripts, and the other TGF\u03b2 superfamily transcripts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings highlight aspects of the complex challenge faced while seeking therapeutic targets to enable tumour spread restriction. However, these outcomes reinforce knowledge that TGF\u03b2 family members can influence seminoma fate and provide new evidence of their potential contribution to the transition of GCNIS cells into tumours.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70100","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T08:44:12Z","timestamp":1753173852000},"page":"210-227","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Spatial transcriptomics mapping of immune cell and TGF\u03b2 signalling pathway heterogeneity in testicular germ cell tumours"],"prefix":"10.1111","volume":"14","author":[{"given":"Sarah C.","family":"Moody","sequence":"first","affiliation":[{"name":"Centre for Reproductive Health Hudson Institute of Medical Research  Clayton Victoria Australia"},{"name":"Department of Molecular and Translational Sciences, School of Clinical Sciences Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Fietz","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Anatomy, Histology and Embryology Justus\u2010Liebig University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedict","family":"Nathaniel","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health Hudson Institute of Medical Research  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Frydenberg","sequence":"additional","affiliation":[{"name":"Department of Surgery FMNHS, Monash\u00a0University  Melbourne Victoria Australia"},{"name":"Department of Urology, Cabrini Institute Cabrini Health  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Tran","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Peter MacCallum Cancer Centre  Melbourne Victoria Australia"},{"name":"Division of Personalised Medicine Walter and Eliza Hall Institute  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans\u2010Christian","family":"Schuppe","sequence":"additional","affiliation":[{"name":"Department of Urology, Pediatric Urology and Andrology Justus Liebig University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate L.","family":"Loveland","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health Hudson Institute of Medical Research  Clayton Victoria Australia"},{"name":"Department of Molecular and Translational Sciences, School of Clinical Sciences Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32810"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2022.11.023"},{"key":"e_1_2_9_4_1","unstructured":"OrganisationWH.International Agency for Research on Cancer. 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