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Glioblastoma stem cells induce quiescence in surrounding neural stem cells via Notch signaling

Katerina Lawlor1, Maria Angeles Marques-Torrejon2, Gopuraja Dharmalingham3

  • 1National Heart and Lung Institute, Imperial College London, London W12 0NN, United Kingdom.

Genes & Development
|November 13, 2020
PubMed

Insights

Transformed neural stem cells (NSCs) resist growth arrest and surprisingly induce quiescence in normal neighboring NSCs. This suggests oncogenic mutations spread in the stem cell niche by inhibiting normal cell proliferation.

Area of Science:

  • Neuroscience
  • Cancer Biology
  • Stem Cell Biology

Background:

  • Adult neural stem cells (NSCs) are increasingly implicated as the cell of origin for glioblastoma.
  • Understanding the interactions within the stem cell niche is crucial for deciphering glioblastoma development.

Purpose of the Study:

  • To analyze the interaction between transformed and wild-type adult neural stem cells (NSCs).
  • To investigate the mechanisms by which oncogenic mutations may propagate within the neural stem cell niche.

Main Methods:

  • Isolation of transformed and wild-type NSCs from the adult mouse subventricular zone niche.
  • Analysis of cell-cell contact and Notch signaling pathways in NSC interactions.

Main Results:

  • Transformed NSCs were found to be resistant to signals that induce quiescence.
  • Transformed NSCs actively induced quiescence in surrounding wild-type NSCs.
  • This induction of quiescence was dependent on cell-cell contact and Notch signaling.

Conclusions:

  • Oncogenic mutations may propagate in the stem cell niche through mechanisms beyond cell-intrinsic advantages.
  • Transformed NSCs can outcompete neighboring stem cells by repressing their proliferation.
  • These findings offer new insights into glioblastoma initiation and progression within the stem cell niche.
Keywords:
Notchcell competitionglioblastomaneural stem cellsquiescence

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