RT Journal Article
SR Electronic
T1 Glioblastoma stem cells induce quiescence in surrounding neural stem cells via Notch signalling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 856062
DO 10.1101/856062
A1 Katerina Lawlor
A1 Maria Angeles Marques-Torrejon
A1 Gopuraja Dharmalingham
A1 Yasmine El-Azhar
A1 Michael D. Schneider
A1 Steven M. Pollard
A1 Tristan A. Rodríguez
YR 2019
UL http://biorxiv.org/content/early/2019/11/26/856062.abstract
AB There is increasing evidence suggesting that adult neural stem cells (NSCs) are a cell of origin of glioblastoma, the most aggressive form of malignant glioma. The earliest stages of hyperplasia are not easy to explore, but likely involve a cross-talk between normal and transformed NSCs. How normal cells respond to this cross-talk and if they expand or are outcompeted is poorly understood. Here we have analysed the interaction of transformed and wild-type NSCs isolated from the adult mouse subventricular zone neural stem cell niche. We find that transformed NSCs are refractory to quiescence-inducing signals. Unexpectedly, however, we also demonstrate that these cells induce a quiescent-like state in surrounding wild-type NSC. We find that this response is cell-cell contact-dependent and that transformed cells activate the Notch pathway in adjacent wild-type NSCs, an event that stimulates their entry into quiescence. Our findings therefore suggest that oncogenic mutations may be propagated in the stem cell niche not just though cell-intrinsic advantages, but also by outcompeting neighbouring stem cells through signalling repression of their proliferation.