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 therap
Chromatin based control of germ cell and early embryonic development in mice
The aim of this course is to provide an overview of epigenetic mechanisms and their link to chromatin dynamics. The different functions of the nucleus involving the genome and its organization will be discussed with an emphasis on technological limits and the new experimental approaches being developed today. Links between the disruption of nuclear functions and the development of human pathologies will be discussed.
The success of the course relies on the active contribution of participants who are expected to be proactive and to participate in all of the events organized including:
i) presentation of their own scientific project with a poster
ii) participation in the Journal Club to both present and review key articles proposed by the speakers,
iii) participation to the “career development” workshop during the Saturday morning and the “epi-Courses” such as the “Art & Science” workshop.
A special session will be devoted to 2 or 3 alumni who have gone on to successful careers in the field of Epigenetics. Everything is in English.