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

First Author  Visvanathan A Year  2024
Journal  Cell PubMed ID  38971152
Mgi Jnum  J:352022 Mgi Id  MGI:7704945
Doi  10.1016/j.cell.2024.06.011 Citation  Visvanathan A, et al. (2024) Early rhombic lip Protogenin(+ve) stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma. Cell
abstractText  We identify a population of Protogenin-positive (PRTG(+ve)) MYC(high) NESTIN(low) stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RL(VZ)). 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 RL(VZ), 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(high) 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(VZ) PRTG(+ve) stem cells inhabiting a specific perivascular niche. Targeting the PRTG(high) compartment and/or the perivascular niche represents an approach to treat children with Gr3-MB.
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