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DOI 10.1016/j.cell.2024.06.011

Медицинская библиотека · Cell · 2024

Early rhombic lip Protogenin+ve stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma.

Visvanathan Abhirami, Saulnier Olivier, Chen Chuan, Haldipur Parthiv, Orisme Wilda, Delaidelli Alberto, Shin Seungmin, Millman Jake, Bryant Andrew, Abeysundara Namal, Wu Xujia, Hendrikse Liam D, Patil Vikas, Bashardanesh Zahedeh, Golser Joseph, Livingston Bryn G, Nakashima Takuma, Funakoshi Yusuke, Ong Winnie, Rasnitsyn Alexandra, Aldinger Kimberly A, Richman Cory M, Van Ommeren Randy, Lee John J Y, Ly Michelle, Vladoiu Maria C, Kharas Kaitlin, Balin Polina, Erickson Anders W, Fong Vernon, Zhang Jiao, Suárez Raúl A, Wang Hao, Huang Ning, Pallota Jonelle G, Douglas Tajana, Haapasalo Joonas, Razavi Ferechte, Silvestri Evelina, Sirbu Olga, Worme Samantha, Kameda-Smith Michelle M, Wu Xiaochong, Daniels Craig, MichaelRaj Antony K, Bhaduri Aparna, Schramek Daniel, Suzuki Hiromichi, Garzia Livia, Ahmed Nabil, Kleinman Claudia L, Stein Lincoln D, Dirks Peter, Dunham Christopher, Jabado Nada, Rich Jeremy N, Li Wei, Sorensen Poul H, Wechsler-Reya Robert J, Weiss William A, Millen Kathleen J, Ellison David W, Dimitrov Dimiter S, Taylor Michael D

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Аннотация

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.

Для цитирования: Visvanathan Abhirami, Saulnier Olivier, Chen Chuan, Haldipur Parthiv, Orisme Wilda, Delaidelli Alberto, Shin Seungmin, Millman Jake, Bryant Andrew, Abeysundara Namal, Wu Xujia, Hendrikse Liam D, Patil Vikas, Bashardanesh Zahedeh, Golser Joseph, Livingston Bryn G, Nakashima Takuma, Funakoshi Yusuke, Ong Winnie, Rasnitsyn Alexandra, Aldinger Kimberly A, Richman Cory M, Van Ommeren Randy, Lee John J Y, Ly Michelle, Vladoiu Maria C, Kharas Kaitlin, Balin Polina, Erickson Anders W, Fong Vernon, Zhang Jiao, Suárez Raúl A, Wang Hao, Huang Ning, Pallota Jonelle G, Douglas Tajana, Haapasalo Joonas, Razavi Ferechte, Silvestri Evelina, Sirbu Olga, Worme Samantha, Kameda-Smith Michelle M, Wu Xiaochong, Daniels Craig, MichaelRaj Antony K, Bhaduri Aparna, Schramek Daniel, Suzuki Hiromichi, Garzia Livia, Ahmed Nabil, Kleinman Claudia L, Stein Lincoln D, Dirks Peter, Dunham Christopher, Jabado Nada, Rich Jeremy N, Li Wei, Sorensen Poul H, Wechsler-Reya Robert J, Weiss William A, Millen Kathleen J, Ellison David W, Dimitrov Dimiter S, Taylor Michael D. Early rhombic lip Protogenin+ve stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma.. Cell. 2024. DOI: 10.1016/j.cell.2024.06.011.

Предметные рубрики MeSH

HumansMedulloblastomaAnimalsNeoplastic Stem CellsMiceRhombencephalonCerebellar NeoplasmsEndothelial CellsStem Cell NicheStem CellsCoculture TechniquesMetencephalon
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