Self-renewal and differentiation of epithelia

 Philippe JAY

 IGF - UMR 5203/U 661

 141, rue de la Cardonille, 34396 Montpellier

Phone: +33 4 34 35 92 98

Email: philippe.jay@igf.cnrs.fr

Website

Our team is interested in the function of the intestinal epithelium as a dynamic barrier that separates our organism from the external environment, its regulation by both luminal (microbiota, pathogens, parasites, mutagens) and stromal (fibroblasts, immune cells, nerve cells) clues, and how alterations of this epithelium functions can lead to diseases including chronic inflammation, autoimmune diseases or cancer. We are particularly interested by the function of the intestinal tuft cells, for which we recently discovered the first function in initiating type 2 immune responses following helminth parasite infections in the gut lumen. This revealed an additional level of functional cooperation between epithelial and hematopoietic compartments to mount an efficient defence against invading organisms. We are also investigating the mechanisms underlying the rapid cellular turnover of the intestinal epithelium, including stem cell maintenance and differentiation into specialized cell types, and how this dynamics is altered during the transition to cancer. With a better understanding of the dynamic ecosystem of intestinal epithelial cells, the ultimate goal of our studies is to propose new approaches to treat or prevent intestinal pathologies and related syndromes.

Keywords: Intestinal epithelium, tuft cells, epithelial turnover, colon cancer, helminth parasites

Main publications

• Gerbe F. and Jay P. : Intestinal tuft cells: epithelial sentinels linking luminal cues to the immune system. Mucosal Immunology, in press (2016).
• Gerbe F., Sidot E., Smyth D. J., Ohmoto M., Matsumoto I., Dardalhon V., Cesses P., Garnier L., Pouzolles M., Brulin B., Bruschi M., Harcus Y., Zimmermann V. S., Taylor N., Maizels  R. M. and Jay P. : Intestinal epithelial tuft cells initiate type 2 mucosal responses to helminth parasites. Nature, vol. 529 : 226-230 (2016).
• Gerbe F., Legraverend C. and Jay P. : The intestinal epithelium tuft cells: specification and function. Cellular and Molecular Life Sciences, vol. 69(17) : 2907-2917 (2012).
• 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 intestional epithelium. The Journal of Cell Biology, vol. 192(5) : 767-780 (2011). See editorial comment on this article on page 706 of the same issue.
  
• Escobar 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, vol. 2 : 258 (2011).
• 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 and is required for Paneth cell differentiation in the intestinal epithelium. The Journal of Cell Biology, vol. 178 (4) : 635-648 (2007).
• van Es J.H., Jay P., Gregorieff A., Jonkheer S., Taketo M.M. and Clevers H. : Wnt signaling induces maturation of Paneth cells in intestinal crypts. Nature Cell Biology, vol. 7(4) : 381-386 (2005).    (Jay P.: co-premier auteur)
• Blache P., van de Wetering M., Duluc I., Domon-Dell C., Berta P., Freund J.-N., Clevers H. and Jay P. : SOX9 is an intestine crypt transcription factor, Is Regulated by the Wnt pathway and represses the CDX-2 and MUC-2 genes. The Journal of Cell Biology, vol. 166 (1) : 37-47 (2004).