Philippe JAY group: SELF-RENEWAL AND DIFFERENTIATION OF EPITHELIA
Departement: Cancer biology - Research axis: Molecular & cellular networks

Julie PANNEQUIN group: SIGNALING, PLASTICITY AND CANCER
Department: Cancer biology - Research axis: Translational biology

JAY group: Research subject

We use the intestinal epithelium as a model to study the key properties of epithelia with rapid turnover, and their alterations in cancer and chronic inflammatory diseases.

We are studying the gene networks and signalling pathways involved in the maintenance and differentiation of the intestinal epithelial stem cells, and in the function of differentiated cells regulating the interface between the host and its environment. Our experimental approach relies on a combination of mouse genetics, molecular and cellular biology and analyses at the pan-genomic scale.

Function of the Sox9 transcription factor: Paneth cells represent one of the differentiated cell types of the intestinal epithelium and secrete antimicrobial peptides regulating the intestinal microflora. We have been interested in the function of Sox9, which is strongly expressed in stem and Paneth cells (Blache et al., J. Cell Biol. 2004), as well as in tuft cells (Gerbe et al., J. Cell Biol. 2011). Constitutive deletion of the Sox9 gene in the intestinal epithelium causes ablation of the Paneth cell lineage (Bastide et al., J. Cell Biol. 2007). Our current objective is to understand the function of Sox9 in Paneth cells and stem cells.

Stem cells and cancer: Although the precise identity of the intestinal epithelium stem cells is still controversial, Lgr5-expressing cells at the crypt bottom have all the features expected from stem cells. We analysed the mode of chromosome segregation in intestinal epithelial stem cells and came to the conclusion that intestinal epithelial stem cells segregate their chromosomes randomly (Escobar et al, Nature Communications 2011). Additional projects are underway to understand the molecular bases of tumorigenesis.

Function of tuft cells: Their unique morphology led to the identification of tuft cells (also called brush cells) more than half a century ago. Because of the lack of appropriate markers, they have since remained overlooked in functional studies of the intestinal epithelium.

We have recently characterised mouse and human intestinal epithelial tuft cells. These rare cells express the DCLK1 marker, previously considered as a putative quiescent stem cell marker in the intestinal epithelium (Gerbe et al., Gastroenterology 2009, vol. 137: 2179). We demonstrated that DCLK1+ cells are instead post-mitotic tuft cells, which are short lived and permanently renewed from Lgr5+ stem cells. According to their unique genetic requirements to differentiate, we proposed that tuft cells constitute a fifth differentiated cell type in the intestinal epithelium (Gerbe et al., J. Cell Biol. 2011, vol. 192: 767-780).

 

 

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LINK TO TEAM WEB SITE

LINK TO THE GIStem consortium homepage

PANNEQUIN group: Research subject

Since cancer has been considered for ages as a disease of proliferation, identification of cancer stem cells has considerably changed this dogma. Cancer Stem Cells (CSC) represent a subpopulation of tumoral cells endowed with self-renewal, tumor initiation and resistance capacities. In the team we are focused on their signaling pathways and plasticity and we are studying more precisely their involvement in tumor recurrence in colorectal cancer. Our research is organized within 3 main axes. The first axis is focused on the deciphering of mechanisms explaining CSC chemoresistance in the aim of identifying innovative strategies to sensitize CSC to these drugs. The second axis proposes to study CSC plasticity through the angle of translational control, and especially by studying RNA modifications (epitranscriptome). Finally, tumoral dissemination is the topic of the third axis with a special focus on the circulating tumor cell characterization, early dissemination and tumor dormancy.

We develop and use cutting edge technologic tools such as “ribosome profiling” and “methylated RNA immunoprecipitation sequencing”(MeRIP-seq). We have established a library of patient derived cell lines from primary tumor, liver metastasis and blood. The team has now acquired a real expertise in the use of mouse models (xenografts and transgenic mice) and patient biopsies thanks to close collaborations with local hospitals (Nîmes and Montpellier). Translational research is always a priority in our research and this is highlighted not only by the development of innovative therapies and clinical tools but also by the presence of Dr Samalin (Digestive Oncologist, ICM) recently welcomed in the team. Finally, our team is highly involved in the SUNRiSE network, which federate several French teams focusing on cancer stem cells in solid tumors.

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Team

Team leader

Philippe Jay
DR2, Inserm


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  04 34 35 92 98

 

Staff Jay/Jay

Tiffany Campion
Master 1, CNRS


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Nathalie Coutry
CRCN, Inserm


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Laure Garnier
IE CDD, CNRS


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François Gerbe
CRCN, CNRS


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Alicia Giordano
Master 2, CNRS


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Marième Ndjim
Post-doctorant(e), UM


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Julie Nguyen
Doctorant(e), UM


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Emmanuelle Sidot
Doctorant(e), UM


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Elisabeth Simboeck
Post-doctorant(e), CNRS


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  04 34 35 92 98

 

Staff Jay/Pannequin

Lucile Bansard
AI CDD, CNRS


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Amandine Bastide
Post-doctorant(e), Inserm


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Guillaume Belthier
Doctorant(e), CNRS


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Caroline Bonnans
CRCN, Inserm


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Armelle Choquet
MCF, UM


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Philippe Crespy
TCN, UM


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Alexandre David
CRCN, Inserm


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Bénédicte Dréan
AI CDD, CNRS


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Alessandro Giammona
Post-doctorant(e), UM


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  04 34 35 92 36

 

Hélène Guillorit
Doctorant(e), UM


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  04 34 35 92 65

 

Francoise Macari
MCF, UM


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  04 34 35 92 67

 

Élisa Moutin
Master 1, CNRS


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Julie Pannequin
CRCN, CNRS


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Jean-Marc Pascussi
CRCN, Inserm


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  04 34 35 92 36

 

Chris Planque
MCF, UM


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  04 34 35 92 36

 

Sébastien Relier
Doctorant(e), UM


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  04 34 35 92 67

 

Anaïs Riviere
Licence pro, UM


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Olivia Villeronce
Doctorant(e), UM


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  04 34 35 93 21

 

Jihane Vitre
IE CDD, CNRS


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JAY group: Major publications

  • Gerbe F., Legraverend C. and Jay P. : The intestinal epithelium tuft cells: specification and function. Cellular and Molecular Life Sciences, 69(17) : 2907-2917 (2012).
  • Ecobar M., Nicolas P., Sangar F., Laurent-Chabalier S., Clair P., Joubert D., Jay P. and Legraverend C. : Intestinal epithelial stem cells do not protect a copy of their genome by asymmetric chromosome segregation. Nature Communications, 2 : 258 (2011).
  • Gerbe F., van Es J. H., Makrini L., Brulin B., Mellitzer G., Robine S., Romagnolo B., Shroyer N. F., Bourgaux J.-F., Pignodel C., Clevers H. and Jay P. : Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium. The Journal of Cell Biology, vol. 192(5) : 767-780 (2011). Commentaire éditorial en page 706.
  • Gerbe F., Brulin B., Makrini L., Legraverend C. and Jay P. : DCAMKL-1 expression identifies tuft cells rather than stem cells in the adult mouse intestinal epithelium. Gastroenterology, vol. 137(6) : 2179-2180 (2009).
  • Bastide P., Darido C., Pannequin J., Kist R., Robine S., Marty-Double C., Bibeau F., Scherer G., Joubert D., Hollande F., Blache P. and Jay P. : Sox9 regulates cell proliferation ans is required for Paneth cell differentiation in the intestinal epithelium. The Journal of Cell Biology, vol. 178 (4) : 635-648 (2007).


PANNEQUIN group: Major publications

  • Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture. Grillet F, Bayet E, Villeronce O, Zappia L, Lagerqvist EL, Lunke S, Charafe-Jauffret E, Pham K, Molck C, Rolland N, Bourgaux JF, Prudhomme M, Philippe C, Bravo S, Boyer JC, Canterel-Thouennon L, Taylor GR, Hsu A, Pascussi JM, Hollande F, Pannequin J. Gut. 2017 Oct;66(10):1802-1810.

  • Pregnane X-receptor promotes stem cell-mediated colon cancer relapse. Planque C, Rajabi F, Grillet F, Finetti P, Bertucci F, Gironella M, Lozano JJ, Beucher B, Giraud J, Garambois V, Vincent C, Brown D, Caillo L, Kantar J, Pelegrin A, Prudhomme M, Ripoche J, Bourgaux JF, Ginestier C, Castells A, Hollande F, Pannequin J, Pascussi JM. Oncotarget. 2016 Aug 30;7(35):56558-56573.

  • Autocrine Secretion of Progastrin Promotes the Survival and Self-Renewal of Colon Cancer Stem-like Cells. Giraud J, Failla LM, Pascussi JM, Lagerqvist EL, Ollier J, Finetti P, Bertucci F, Ya C, Gasmi I, Bourgaux JF, Prudhomme M, Mazard T, Ait-Arsa I, Houhou L, Birnbaum D, Pélegrin A, Vincent C, Ryall JG, Joubert D, Pannequin J, Hollande F. Cancer Res. 2016 Jun 15;76(12):3618-28.

  • Antibiotics inhibit sphere-forming ability in suspension culture. Relier S, Yazdani L, Ayad O, Choquet A, Bourgaux JF, Prudhomme M, Pannequin J, Macari F, David A. Cancer Cell Int. 2016 Feb 12;16:6. doi: 10.1186/s12935-016-0277-6

  • TRM6/61 connects PKCα with translational control through tRNAi(Met) stabilization: impact on tumorigenesis. Macari F, El-Houfi Y, Boldina G, Xu H, Khoury-Hanna S, Ollier J, Yazdani L, Zheng G, Bièche I, Legrand N, Paulet D, Durrieu S, Byström A, Delbecq S, Lapeyre B, Bauchet L, Pannequin J, Hollande F, Pan T, Teichmann M, Vagner S, David A, Choquet A, Joubert D. Oncogene. 2016 Apr 7;35(14):1785-96.
 

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