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Life Science Alliance, Life Science Alliance, 2(2), p. e201800218, 2019

DOI: 10.26508/lsa.201800218

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Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven tumorigenesis

This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

Neural stem/progenitor cells (NSPCs) of the ventricular–subventricular zone (V-SVZ) are candidate cells of origin for many brain tumors. However, whether NSPCs in different locations within the V-SVZ differ in susceptibility to tumorigenic mutations is unknown. Here, single-cell measurements of signal transduction intermediates in the mechanistic target of rapamycin complex 1 (mTORC1) pathway reveal that ventral NSPCs have higher levels of signaling than dorsal NSPCs.These features are linked with differences in mTORC1-driven disease severity: introduction of a pathognomonicTsc2mutation only results in formation of tumor-like masses from the ventral V-SVZ. We propose a direct link between location-dependent intrinsic growth properties imbued by mTORC1 and predisposition to tumor development.