加拿大病童医院Michael D. Taylor和美国匹兹堡大学医学院Dimiter S. Dimitrov共同合作，近期取得重要工作进展。他们研究提出，人特有神经血管生态位中的早期菱形唇Protogenin+ve干细胞引发并维持3型髓母细胞瘤。相关研究成果2024年7月5日在线发表于《细胞》杂志上。
研究人员在四周大的人类胚胎后脑中鉴定出一群Protogenin阳性（PRTG+ve）MYChigh NESTINlow干细胞，这些干细胞随后定位于菱形唇（RLVZ）的心室区。早期Prtg+ve菱形唇干细胞的肿瘤转化可引发类似3型髓母细胞瘤（Gr3-MB）样肿瘤。PRTG+ve干细胞在RLVZ中与人类特异性介入的中间血管丛相邻生长，这种表型在Gr3-MB中重现，但在其他类型的髓母细胞瘤中没有。
Gr3-MB与内皮细胞共培养促进肿瘤干细胞生长，内皮细胞呈现不成熟表型。使用白喉毒素系统或嵌合抗原受体T细胞，在体内靶向Gr3-MB的PRTGhigh区室构成了有效的治疗。人Gr3-MB可能来源于，栖息在特定血管周围生态位的早期胚胎RLVZ-PRTG+ve干细胞。
总之，这一研究表明，靶向PRTGhigh区室或血管周围生态位是治疗儿童Gr3-MB的一种方法。
附：英文原文
Title: Early rhombic lip Protogenin+ve stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma
Author: 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 Badhuri, Daniel Schramek, Hiromichi Suzuki, Livia Garzia, Nabil Ahmed, Claudia L. Kleinman
Issue&Volume: 2024-07-05
Abstract: 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.
DOI: 10.1016/j.cell.2024.06.011
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00651-2