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

ABSTRACT: 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 eit

SUBMITTER: Visvanathan A 

PROVIDER: S-EPMC11707800 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature