Publications récentes

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

Larissa Mourao, Guillaume Jacquemin, Mathilde Huyghe, Wojciech J. Nawrocki, Naoual Menssouri, Nicolas Servant, Silvia Fre Scientific Reports volume 9, Article number: 888 (2019), DOI:10.1038/s41598-018-37301-3 En savoir plus Replier

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

Développement et Epigenèse High-resolution visualization of H3 variants during replication reveals their controlled recycling.

Clément C, Orsi GA, Gatto A, Forest A, Hajj H, Miné-Hattab J, Garnier M, Gurard-Levin ZA, Quivy JP and Almouzni G Nature Commun. - Dedicated to Maxime Dahan En savoir plus Replier

 9(1):3181. doi: 10.1038/s41467-018-05697-1.

Cellules souches et potentiel Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland

Lilja, A., Rodilla, V., Huyghe, M., Hannezo, E., Landragin, C., Renaud, O., Leroy, O., Ruland, S., Simons, B.D, and Fre, S. Nat Cell Biol. May 21, 2018. doi:10.1038/s41556-018-0108-1 En savoir plus Replier

Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer.

News and Views:  Mammary lineage restriction in development. Philip Bland & Beatrice A. Howard.