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

First Author  Mourao L Year  2019
Journal  Sci Rep Volume  9
Issue  1 Pages  888
PubMed ID  30696875 Mgi Jnum  J:306824
Mgi Id  MGI:6717679 Doi  10.1038/s41598-018-37301-3
Citation  Mourao L, et al. (2019) Lineage tracing of Notch1-expressing cells in intestinal tumours reveals a distinct population of cancer stem cells. Sci Rep 9(1):888
abstractText  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.
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