Tailless/TLX reverts intermediate neural progenitors to stem cells driving tumourigenesis via repression of asense/ASCL1
Publication Date
2020-02-19Journal Title
eLife
Publisher
eLife Sciences Publications, Ltd
Volume
9
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Hakes, A. E., & Brand, A. H. (2020). Tailless/TLX reverts intermediate neural progenitors to stem cells driving tumourigenesis via repression of asense/ASCL1. eLife, 9 https://doi.org/10.7554/elife.53377
Description
Funder: Royal Society; FundRef: http://dx.doi.org/10.13039/501100000288
Abstract
Understanding the sequence of events leading to cancer relies in large part upon identifying the tumour cell of origin. Glioblastoma is the most malignant brain cancer but the early stages of disease progression remain elusive. Neural lineages have been implicated as cells of origin, as have glia. Interestingly, high levels of the neural stem cell regulator TLX correlate with poor patient prognosis. Here we show that high levels of the Drosophila TLX homologue, Tailless, initiate tumourigenesis by reverting intermediate neural progenitors to a stem cell state. Strikingly, we could block tumour formation completely by re-expressing Asense (homologue of human ASCL1), which we show is a direct target of Tailless. Our results predict that expression of TLX and ASCL1 should be mutually exclusive in glioblastoma, which was verified in single-cell RNA-seq of human glioblastoma samples. Counteracting high TLX is a potential therapeutic strategy for suppressing tumours originating from intermediate progenitor cells.
Keywords
Research Article, Developmental Biology, Stem Cells and Regenerative Medicine, neural stem cell, glioblastoma, tumourigenesis, tailless, TLX, dedifferentiation, D. melanogaster
Sponsorship
Wellcome (103792)
Wellcome (102454)
Wellcome (092096)
Cancer Research UK (C6946/A14492)
Identifiers
53377
External DOI: https://doi.org/10.7554/elife.53377
This record's URL: https://www.repository.cam.ac.uk/handle/1810/303099
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.