Abhirami Visvanathan, Olivier Saulnier, Chuan Chen, Parthiv Haldipur, Wilda Orisme, Alberto Delaidelli, Seungmin Shin, Jake Millman, Andrew Bryant, Namal Abeysundara, Xujia Wu, Liam D Hendrikse, Vikas Patil, Zahedeh Bashardanesh, Joseph Golser, Bryn G Livingston, Takuma Nakashima, Yusuke Funakoshi, Winnie Ong, Alexandra Rasnitsyn, Kimberly A Aldinger, Cory M Richman, Randy Van Ommeren, John J Y Lee, Michelle Ly, Maria C Vladoiu, Kaitlin Kharas, Polina Balin, Anders W Erickson, Vernon Fong, Jiao Zhang, Raúl A Suárez, Hao Wang, Ning Huang, Jonelle G Pallota, Tajana Douglas, Joonas Haapasalo, Ferechte Razavi, Evelina Silvestri, Olga Sirbu, Samantha Worme, Michelle M Kameda-Smith, Xiaochong Wu, Craig Daniels, Antony K MichaelRaj, Aparna Bhaduri, Daniel Schramek, Hiromichi Suzuki, Livia Garzia, Nabil Ahmed, Claudia L Kleinman, Lincoln D Stein, Peter Dirks, Christopher Dunham, Nada Jabado, Jeremy N Rich, Wei Li, Poul H Sorensen, Robert J Wechsler-Reya, William A Weiss, Kathleen J Millen, David W Ellison, Dimiter S Dimitrov, Michael D Taylor
{"title":"人类特异性神经血管龛中的早期菱形脂质Protogenin+ve干细胞启动并维持了第3组髓母细胞瘤。","authors":"Abhirami Visvanathan, Olivier Saulnier, Chuan Chen, Parthiv Haldipur, Wilda Orisme, Alberto Delaidelli, Seungmin Shin, Jake Millman, Andrew Bryant, Namal Abeysundara, Xujia Wu, Liam D Hendrikse, Vikas Patil, Zahedeh Bashardanesh, Joseph Golser, Bryn G Livingston, Takuma Nakashima, Yusuke Funakoshi, Winnie Ong, Alexandra Rasnitsyn, Kimberly A Aldinger, Cory M Richman, Randy Van Ommeren, John J Y Lee, Michelle Ly, Maria C Vladoiu, Kaitlin Kharas, Polina Balin, Anders W Erickson, Vernon Fong, Jiao Zhang, Raúl A Suárez, Hao Wang, Ning Huang, Jonelle G Pallota, Tajana Douglas, Joonas Haapasalo, Ferechte Razavi, Evelina Silvestri, Olga Sirbu, Samantha Worme, Michelle M Kameda-Smith, Xiaochong Wu, Craig Daniels, Antony K MichaelRaj, Aparna Bhaduri, Daniel Schramek, Hiromichi Suzuki, Livia Garzia, Nabil Ahmed, Claudia L Kleinman, Lincoln D Stein, Peter Dirks, Christopher Dunham, Nada Jabado, Jeremy N Rich, Wei Li, Poul H Sorensen, Robert J Wechsler-Reya, William A Weiss, Kathleen J Millen, David W Ellison, Dimiter S Dimitrov, Michael D Taylor","doi":"10.1016/j.cell.2024.06.011","DOIUrl":null,"url":null,"abstract":"<p><p>We identify a population of Protogenin-positive (PRTG<sup>+ve</sup>) MYC<sup>high</sup> NESTIN<sup>low</sup> stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RL<sup>VZ</sup>). Oncogenic transformation of early Prtg<sup>+ve</sup> rhombic lip stem cells initiates group 3 medulloblastoma (Gr3-MB)-like tumors. PRTG<sup>+ve</sup> stem cells grow adjacent to a human-specific interposed vascular plexus in the RL<sup>VZ</sup>, a phenotype that is recapitulated in Gr3-MB but not in other types of medulloblastoma. Co-culture of Gr3-MB with endothelial cells promotes tumor stem cell growth, with the endothelial cells adopting an immature phenotype. Targeting the PRTG<sup>high</sup> compartment of Gr3-MB in vivo using either the diphtheria toxin system or chimeric antigen receptor T cells constitutes effective therapy. Human Gr3-MBs likely arise from early embryonic RL<sup>VZ</sup> PRTG<sup>+ve</sup> stem cells inhabiting a specific perivascular niche. Targeting the PRTG<sup>high</sup> compartment and/or the perivascular niche represents an approach to treat children with Gr3-MB.</p>","PeriodicalId":9656,"journal":{"name":"Cell","volume":null,"pages":null},"PeriodicalIF":45.5000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Early rhombic lip Protogenin<sup>+ve</sup> stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma.\",\"authors\":\"Abhirami Visvanathan, Olivier Saulnier, Chuan Chen, Parthiv Haldipur, Wilda Orisme, Alberto Delaidelli, Seungmin Shin, Jake Millman, Andrew Bryant, Namal Abeysundara, Xujia Wu, Liam D Hendrikse, Vikas Patil, Zahedeh Bashardanesh, Joseph Golser, Bryn G Livingston, Takuma Nakashima, Yusuke Funakoshi, Winnie Ong, Alexandra Rasnitsyn, Kimberly A Aldinger, Cory M Richman, Randy Van Ommeren, John J Y Lee, Michelle Ly, Maria C Vladoiu, Kaitlin Kharas, Polina Balin, Anders W Erickson, Vernon Fong, Jiao Zhang, Raúl A Suárez, Hao Wang, Ning Huang, Jonelle G Pallota, Tajana Douglas, Joonas Haapasalo, Ferechte Razavi, Evelina Silvestri, Olga Sirbu, Samantha Worme, Michelle M Kameda-Smith, Xiaochong Wu, Craig Daniels, Antony K MichaelRaj, Aparna Bhaduri, Daniel Schramek, Hiromichi Suzuki, Livia Garzia, Nabil Ahmed, Claudia L Kleinman, Lincoln D Stein, Peter Dirks, Christopher Dunham, Nada Jabado, Jeremy N Rich, Wei Li, Poul H Sorensen, Robert J Wechsler-Reya, William A Weiss, Kathleen J Millen, David W Ellison, Dimiter S Dimitrov, Michael D Taylor\",\"doi\":\"10.1016/j.cell.2024.06.011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>We identify a population of Protogenin-positive (PRTG<sup>+ve</sup>) MYC<sup>high</sup> NESTIN<sup>low</sup> stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RL<sup>VZ</sup>). Oncogenic transformation of early Prtg<sup>+ve</sup> rhombic lip stem cells initiates group 3 medulloblastoma (Gr3-MB)-like tumors. PRTG<sup>+ve</sup> stem cells grow adjacent to a human-specific interposed vascular plexus in the RL<sup>VZ</sup>, a phenotype that is recapitulated in Gr3-MB but not in other types of medulloblastoma. Co-culture of Gr3-MB with endothelial cells promotes tumor stem cell growth, with the endothelial cells adopting an immature phenotype. Targeting the PRTG<sup>high</sup> compartment of Gr3-MB in vivo using either the diphtheria toxin system or chimeric antigen receptor T cells constitutes effective therapy. Human Gr3-MBs likely arise from early embryonic RL<sup>VZ</sup> PRTG<sup>+ve</sup> stem cells inhabiting a specific perivascular niche. Targeting the PRTG<sup>high</sup> compartment and/or the perivascular niche represents an approach to treat children with Gr3-MB.</p>\",\"PeriodicalId\":9656,\"journal\":{\"name\":\"Cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":45.5000,\"publicationDate\":\"2024-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cell.2024.06.011\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/5 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2024.06.011","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/5 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Early rhombic lip Protogenin+ve stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma.
We identify a population of Protogenin-positive (PRTG+ve) MYChigh NESTINlow stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RLVZ). Oncogenic transformation of early Prtg+ve rhombic lip stem cells initiates group 3 medulloblastoma (Gr3-MB)-like tumors. PRTG+ve stem cells grow adjacent to a human-specific interposed vascular plexus in the RLVZ, a phenotype that is recapitulated in Gr3-MB but not in other types of medulloblastoma. Co-culture of Gr3-MB with endothelial cells promotes tumor stem cell growth, with the endothelial cells adopting an immature phenotype. Targeting the PRTGhigh compartment of Gr3-MB in vivo using either the diphtheria toxin system or chimeric antigen receptor T cells constitutes effective therapy. Human Gr3-MBs likely arise from early embryonic RLVZ PRTG+ve stem cells inhabiting a specific perivascular niche. Targeting the PRTGhigh compartment and/or the perivascular niche represents an approach to treat children with Gr3-MB.
期刊介绍：
Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO).
The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries.
In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.
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