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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.
Affiliation
  • Visvanathan A; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Saulnier O; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Genomics and Development of Childhood Cancers, Institut Curie, PSL University, 75005 Pari
  • Chen C; Center for Antibody Therapeutics, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Haldipur P; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
  • Orisme W; St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Delaidelli A; British Columbia Cancer Agency, Vancouver, BC, Canada.
  • Shin S; Center for Antibody Therapeutics, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Millman J; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
  • Bryant A; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Abeysundara N; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Wu X; Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Hendrikse LD; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Patil V; MacFeeters-Hamilton Center for Neuro-Oncology Research, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Bashardanesh Z; Lady Davis Institute, McGill University, Montreal, QC, Canada.
  • Golser J; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
  • Livingston BG; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, C
  • Nakashima T; Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
  • Funakoshi Y; Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
  • Ong W; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, C
  • Rasnitsyn A; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Aldinger KA; Departments of Pediatrics and Neurology. University of Washington, Seattle, WA, USA.
  • Richman CM; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Van Ommeren R; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, C
  • Lee JJY; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, C
  • Ly M; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, C
  • Vladoiu MC; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, C
  • Kharas K; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, C
  • Balin P; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, C
  • Erickson AW; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, C
  • Fong V; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, C
  • Zhang J; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Texas Children's Cancer and Hematology Center, Houston, TX, USA; Department of Pediatrics
  • Suárez RA; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Wang H; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Huang N; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Pallota JG; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Douglas T; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
  • Haapasalo J; Department of Neurosurgery, Tampere University Hospital, Tampere, Finland.
  • Razavi F; Assistance Publique Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France.
  • Silvestri E; Surgical Pathology Unit, San Camillo Forlanini Hospital, Rome, Italy.
  • Sirbu O; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Worme S; Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
  • Kameda-Smith MM; Texas Children's Cancer and Hematology Center, Houston, TX, USA; Department of Pediatrics - Hematology/Oncology, Baylor College of Medicine, Houston, TX, USA.
  • Wu X; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Texas Children's Cancer and Hematology Center, Houston, TX, USA; Department of Pediatrics
  • Daniels C; The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada; Texas Children's Cancer and Hematology Center, Houston, TX, USA; Department of Pediatrics
  • MichaelRaj AK; Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Bhaduri A; Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Schramek D; Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
  • Suzuki H; Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
  • Garzia L; Cancer Research Program, McGill University Health Centre Research Institute, Montreal, QC, Canada.
  • Ahmed N; Centre for Cell and Gene Therapy, Texas Children's Hospital, Houston Methodist Hospital, Baylor College of Medicine, Houston, TX, USA.
Cell ; 2024 Jul 05.
Article in En | MEDLINE | ID: mdl-38971152
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cell Year: 2024 Document type: Article
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Cell Year: 2024 Document type: Article