{"title":"PLAG1 在唾液腺导管-针状单元中的过表达会导致具有针状特征的上皮肿瘤:管腔干细胞/祖细胞的肿瘤化可能导致仅由管腔细胞组成的唾液腺肿瘤的发生。","authors":"Yunosuke Ikeda, Rika Yasuhara, Junichi Tanaka, Hiroko Ida-Yonemochi, Haruhiko Akiyama, Keishi Otsu, Ikuya Miyamoto, Hidemitsu Harada, Hiroyuki Yamada, Toshiyuki Fukada, Tarou Irié","doi":"10.1016/j.job.2024.08.002","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Details about salivary gland tumor histogenesis remain unknown. Here, we established a newly generated murine salivary gland tumor model that could overexpress pleomorphic adenoma gene 1 (PLAG1) and attempted to clarify the events that occur during the early phase of salivary gland tumor histogenesis.</p><p><strong>Methods: </strong>Salivary gland tumors were generated using murine models (Sox9IRES-CreERT2; ROSA26-PLAG1). Lineage tracing of Sox9-expressing cells was performed using Sox9IRES-CreERT2; ROSA26-tdTomato mice, which were generated by crossing Sox9<sup>CreERT2/-</sup> and ROSA26-tdTomato mice (expressing the tdTomato fluorescent protein). Organ-cultured embryonic salivary glands from the murine model were morphologically analyzed, and mRNA sequencing was conducted two days after tumor induction for gene enrichment and functional annotation analysis.</p><p><strong>Results: </strong>Salivary gland tumors exhibited epithelial features with acinar-like structures because of gene rearrangements in the luminal cells. Structural disturbances in the duct-acinar unit of the salivary gland were observed and cancer-related pathways were enriched among the differentially upregulated genes in the early phase of tumor induction in an organ-cultured embryonic salivary gland tumor model.</p><p><strong>Conclusions: </strong>The newly generated murine salivary gland tumor model may show that the tumorization of luminal stem/progenitor cells can result in the development of salivary gland tumors comprising only luminal cells.</p>","PeriodicalId":45851,"journal":{"name":"Journal of Oral Biosciences","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PLAG1 overexpression in salivary gland duct-acinar units results in epithelial tumors with acinar-like features: Tumorization of luminal stem/progenitor cells may result in the development of salivary gland tumors consisting of only luminal cells.\",\"authors\":\"Yunosuke Ikeda, Rika Yasuhara, Junichi Tanaka, Hiroko Ida-Yonemochi, Haruhiko Akiyama, Keishi Otsu, Ikuya Miyamoto, Hidemitsu Harada, Hiroyuki Yamada, Toshiyuki Fukada, Tarou Irié\",\"doi\":\"10.1016/j.job.2024.08.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>Details about salivary gland tumor histogenesis remain unknown. Here, we established a newly generated murine salivary gland tumor model that could overexpress pleomorphic adenoma gene 1 (PLAG1) and attempted to clarify the events that occur during the early phase of salivary gland tumor histogenesis.</p><p><strong>Methods: </strong>Salivary gland tumors were generated using murine models (Sox9IRES-CreERT2; ROSA26-PLAG1). Lineage tracing of Sox9-expressing cells was performed using Sox9IRES-CreERT2; ROSA26-tdTomato mice, which were generated by crossing Sox9<sup>CreERT2/-</sup> and ROSA26-tdTomato mice (expressing the tdTomato fluorescent protein). Organ-cultured embryonic salivary glands from the murine model were morphologically analyzed, and mRNA sequencing was conducted two days after tumor induction for gene enrichment and functional annotation analysis.</p><p><strong>Results: </strong>Salivary gland tumors exhibited epithelial features with acinar-like structures because of gene rearrangements in the luminal cells. Structural disturbances in the duct-acinar unit of the salivary gland were observed and cancer-related pathways were enriched among the differentially upregulated genes in the early phase of tumor induction in an organ-cultured embryonic salivary gland tumor model.</p><p><strong>Conclusions: </strong>The newly generated murine salivary gland tumor model may show that the tumorization of luminal stem/progenitor cells can result in the development of salivary gland tumors comprising only luminal cells.</p>\",\"PeriodicalId\":45851,\"journal\":{\"name\":\"Journal of Oral Biosciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2024-08-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Oral Biosciences\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.job.2024.08.002\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Oral Biosciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.job.2024.08.002","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
PLAG1 overexpression in salivary gland duct-acinar units results in epithelial tumors with acinar-like features: Tumorization of luminal stem/progenitor cells may result in the development of salivary gland tumors consisting of only luminal cells.
Objectives: Details about salivary gland tumor histogenesis remain unknown. Here, we established a newly generated murine salivary gland tumor model that could overexpress pleomorphic adenoma gene 1 (PLAG1) and attempted to clarify the events that occur during the early phase of salivary gland tumor histogenesis.
Methods: Salivary gland tumors were generated using murine models (Sox9IRES-CreERT2; ROSA26-PLAG1). Lineage tracing of Sox9-expressing cells was performed using Sox9IRES-CreERT2; ROSA26-tdTomato mice, which were generated by crossing Sox9CreERT2/- and ROSA26-tdTomato mice (expressing the tdTomato fluorescent protein). Organ-cultured embryonic salivary glands from the murine model were morphologically analyzed, and mRNA sequencing was conducted two days after tumor induction for gene enrichment and functional annotation analysis.
Results: Salivary gland tumors exhibited epithelial features with acinar-like structures because of gene rearrangements in the luminal cells. Structural disturbances in the duct-acinar unit of the salivary gland were observed and cancer-related pathways were enriched among the differentially upregulated genes in the early phase of tumor induction in an organ-cultured embryonic salivary gland tumor model.
Conclusions: The newly generated murine salivary gland tumor model may show that the tumorization of luminal stem/progenitor cells can result in the development of salivary gland tumors comprising only luminal cells.