Lineage tracing of Notch1-expressing cells in intestinal tumours reveals a distinct population of cancer stem cells

Colon tumours are hierarchically organized and contain multipotent self-renewing cells, called Cancer Stem Cells (CSCs). We have previously shown that the Notch1 receptor is expressed in Intestinal Stem Cells (ISCs); given the critical role played by Notch signalling in promoting intestinal tumourig...

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Bibliographic Details
Published in:Scientific reports 2019-01, Vol.9 (1), p.888-888, Article 888
Main Authors: Mourao, Larissa, Jacquemin, Guillaume, Huyghe, Mathilde, Nawrocki, Wojciech J., Menssouri, Naoual, Servant, Nicolas, Fre, Silvia
Format: Article
Language:English
Subjects:
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Biochemistry, Molecular Biology
Cancer
Cell self-renewal
Colon
Colon cancer
Genomics
Humanities and Social Sciences
Intestine
Life Sciences
multidisciplinary
Notch1 protein
Science
Science (multidisciplinary)
Stem cells
Transcription
Tumorigenesis
Tumors
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Summary:Colon tumours are hierarchically organized and contain multipotent self-renewing cells, called Cancer Stem Cells (CSCs). We have previously shown that the Notch1 receptor is expressed in Intestinal Stem Cells (ISCs); given the critical role played by Notch signalling in promoting intestinal tumourigenesis, we explored Notch1 expression in tumours. Combining lineage tracing in two tumour models with transcriptomic analyses, we found that Notch1+ tumour cells are undifferentiated, proliferative and capable of indefinite self-renewal and of generating a heterogeneous clonal progeny. Molecularly, the transcriptional signature of Notch1+ tumour cells highly correlates with ISCs, suggestive of their origin from normal crypt cells. Surprisingly, Notch1+ expression labels a subset of CSCs that shows reduced levels of Lgr5, a reported CSCs marker. The existence of distinct stem cell populations within intestinal tumours highlights the necessity of better understanding their hierarchy and behaviour, to identify the correct cellular targets for therapy.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-37301-3