Language

English

Publication Date

8-22-2024

Journal

Cell

DOI

10.1016/j.cell.2024.06.011

PMID

38971152

PMCID

PMC11707800

PubMedCentral® Posted Date

1-8-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

We identify a population of 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 initiate 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 which is recapitulated in Gr3-MB, but not 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 either the PRTGhigh compartment, and/or the perivascular niche represents an approach to treat children with Gr3-MB.

Keywords

Humans, Medulloblastoma, Animals, Neoplastic Stem Cells, Mice, Rhombencephalon, Cerebellar Neoplasms, Endothelial Cells, Stem Cell Niche, Stem Cells, Coculture Techniques, Embryonic Structures, Metencephalon, Rhombic lip, cancer genomics, perivascular niche, Group 3 medulloblastoma, brain tumor immunotherapy

Published Open-Access

yes

Download

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.