Cell-of-origin susceptibility to glioblastoma formation declines with neural lineage restriction Journal Article


Authors: Alcantara Llaguno, S.; Sun, D.; Pedraza, A. M.; Vera, E.; Wang, Z.; Burns, D. K.; Parada, L. F.
Article Title: Cell-of-origin susceptibility to glioblastoma formation declines with neural lineage restriction
Abstract: The contribution of lineage identity and differentiation state to malignant transformation is controversial. We have previously shown that adult neural stem and early progenitor cells give origin to glioblastoma. Here we systematically assessed the tumor-initiating potential of adult neural populations at various stages of lineage progression. Cell type–specific tamoxifen-inducible Cre recombinase transgenes were used to target glioblastoma-relevant tumor suppressors Nf1, Trp53 and Pten in late-stage neuronal progenitors, neuroblasts and differentiated neurons. Mutant mice showed cellular and molecular defects demonstrating the impact of tumor suppressor loss, with mutant neurons being the most resistant to early changes associated with tumor development. However, we observed no evidence of glioma formation. These studies show that increasing lineage restriction is accompanied by decreasing susceptibility to malignant transformation, indicating a glioblastoma cell-of-origin hierarchy in which stem cells sit at the apex and differentiated cell types are least susceptible to tumorigenesis. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Journal Title: Nature Neuroscience
Volume: 22
Issue: 4
ISSN: 1097-6256
Publisher: Nature Publishing Group  
Date Published: 2019-04-01
Start Page: 545
End Page: 555
Language: English
DOI: 10.1038/s41593-018-0333-8
PUBMED: 30778149
PROVIDER: scopus
PMCID: PMC6594191
DOI/URL:
Notes: Article -- Export Date: 1 May 2019 -- Source: Scopus
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MSK Authors
  1. Alicia Maria Pedraza
    20 Pedraza
  2. Elsa Vera
    5 Vera
  3. Luis F Parada
    14 Parada
  4. Zilai Wang
    4 Wang
  5. Daochun Sun
    7 Sun