Reference number : GC-2017-Q1-03057, amendment number : , agreement type : G, recipient legal name : Boudreau, François (Université de Sherbrooke), recipient country : CA, recipient province : nan, recipient city : Quebec|Québec, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : The intestinal epithelium is a dynamic system that constantly and rapidly regenerates throughout the 
organism life. This epithelium is organized in crypt and villus compartments harboring distinct cell 
populations and functions. Intestinal crypts contain epithelial stem cells surrounded by differentiated 
Paneth cells. These latter cells express growth-promoting and cell-protective peptides to ensure 
optimal production of progenitors from the stem cells. Intestinal villi contain differentiated subtypes 
of epithelial cells including enterocytes, goblet and enteroendocrine cells. Although some clues have 
been collected over the past years on the nature of the molecular mechanisms that are required for 
epithelial cell specification and maintenance in this particular context, the exact regulatory circuit 
involved is still not well defined. This renewal of Discovery Grant intends to pursue this program of 
research and proposes to integrate, over the next five years, the interactive transcriptional network 
between a set of proteins including some of which we have studied over the past years. More 
precisely, our proposed work will focus on the GATA4 transcription factor, for which we have 
recently identified specific novel intestinal epithelial cell functions, toward its integrated 
transcriptional and biological impact with the discovery of other relevant transcriptional regulators. 
We also intend to take advantage of an innovative system model that we have recently optimized in 
the laboratory. This biological system consists of mini epithelial guts growing ex vivo that perfectly 
recapitulate proliferation and cytodifferentiation of the intestinal epithelium. This research program 
will aim to define the nature of GATA4 protein complexes susceptible to regulate the intestinal 
epithelial transcriptome in stem and differentiated cells and to define the global intestinal epithelial 
genetic targets of GATA4 in combination to most relevant identified interacting transcription 
regulator(s). It is our hope that these strategies will provide crucial information on the nature of the 
epithelial cell specific transcriptional interactome(s) in both epithelial stem and differentiated cells. 
This will allow a better understanding of the nature of regulators important for intestinal epithelial cell 
specification and perhaps provide novel long-term targeting strategies to alternatively produce 
unique culture sets of enriched and specific subtypes of intestinal epithelial cells, models that still 
await to be optimized., program purpose french : The intestinal epithelium is a dynamic system that constantly and rapidly regenerates throughout the 
organism life. This epithelium is organized in crypt and villus compartments harboring distinct cell 
populations and functions. Intestinal crypts contain epithelial stem cells surrounded by differentiated 
Paneth cells. These latter cells express growth-promoting and cell-protective peptides to ensure 
optimal production of progenitors from the stem cells. Intestinal villi contain differentiated subtypes 
of epithelial cells including enterocytes, goblet and enteroendocrine cells. Although some clues have 
been collected over the past years on the nature of the molecular mechanisms that are required for 
epithelial cell specification and maintenance in this particular context, the exact regulatory circuit 
involved is still not well defined. This renewal of Discovery Grant intends to pursue this program of 
research and proposes to integrate, over the next five years, the interactive transcriptional network 
between a set of proteins including some of which we have studied over the past years. More 
precisely, our proposed work will focus on the GATA4 transcription factor, for which we have 
recently identified specific novel intestinal epithelial cell functions, toward its integrated 
transcriptional and biological impact with the discovery of other relevant transcriptional regulators. 
We also intend to take advantage of an innovative system model that we have recently optimized in 
the laboratory. This biological system consists of mini epithelial guts growing ex vivo that perfectly 
recapitulate proliferation and cytodifferentiation of the intestinal epithelium. This research program 
will aim to define the nature of GATA4 protein complexes susceptible to regulate the intestinal 
epithelial transcriptome in stem and differentiated cells and to define the global intestinal epithelial 
genetic targets of GATA4 in combination to most relevant identified interacting transcription 
regulator(s). It is our hope that these strategies will provide crucial information on the nature of the 
epithelial cell specific transcriptional interactome(s) in both epithelial stem and differentiated cells. 
This will allow a better understanding of the nature of regulators important for intestinal epithelial cell 
specification and perhaps provide novel long-term targeting strategies to alternatively produce 
unique culture sets of enriched and specific subtypes of intestinal epithelial cells, models that still 
await to be optimized., agreement title english : Defining the molecular mechanisms driving intestinal epithelial cell specification, agreement title french : Defining the molecular mechanisms driving intestinal epithelial cell specification, agreement number : RGPIN, agreement value : 250000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada