Isabelle Garcia – Gilbert Vassart

Our research

RESEARCH  

INTESTINAL STEM CELL BIOLOGY

 

The adult gastrointestinal epithelium is a specialized tissue devoted to nutrients sensing and absorption that regulates the “in/out” energy supply for the whole body. This columnar epithelium also constitutes an important barrier against pathogens or environmental toxic agents, concomitantly hosting the microbiota.
Our goal is to bring new insights about the molecular and cellular mechanisms regulating the gastrointestinal epithelium during development, in adult homeostasis or during pathological conditions such as regenerative or oncogenic processes as well as metabolic diseases.
We combine in vivo studies via phenotypical analysis of transgenic knock-in, knockout and lineage tracing Cre recombinase lines with the use of the “3R compliant” ex vivo approach which involves primary culture of mouse intestinal stem cells growing as organoids or “mini-guts”.

Tissue development

We have isolated and characterized fetal intestinal and gastric progenitors using the three dimensional ex vivo culture system and by lineage tracing in vivo. Our results have shown that these epithelia in mammals are generated in two separate waves – a fetal and an adult one – which depend on two different types of stem cells.

Tissu regeneration

We study the various kinds of intestinal stem cells under regenerative conditions induced by different types of tissue damages in order to identify new cell markers with potential interest in the physiopathology of inflammatory bowel disease or Crohn disease.
We have demonstrated that regenerating epithelial cells exhibit a transcriptome very similar to that of fetal progenitors, through a dedifferentiation process occurring in terminally and/or less committed cells.

Transition stages are under study.

GPCRs and Intestinal homeostasis

The Leucine-rich repeat-containing G protein-coupled receptors (Lgr4/Lgr5) are expressed in Intestinal Stem Cells (ISC).
Our group has demonstrated that  the Wnt/b-catenin target Lgr5 controls ISC maturation as well as their capacity to generate their own extracellular matrix through their interaction with the Rspondin 2 ligand.
The role of these receptors in tumor development is under investigation.

Group members

Marie-Isabelle Garcia : Principal Investigator (Marie.Garcia@ulb.ac.be)

phone # +32 (0)2 555 4190

She performed her PhD in Biochemistry at the University Paris VII (France) in 1996 and pursued with a postodoctoral position at the Institut Pasteur (France) where she studied the role of virulence factors in pathogenic E. coli strains. After a postdoctoral training at the University La Sapienza of Rome (Italy) to study viral infection and host specificity (1998-2004). She joined the IRIBHM institute in 2006 and developed research on intestinal stem cells. Since 2017, she also teaches biochemistry at the Faculty of Medecine.

Gilbert Vassart (gvassart@ulb.ac.be)

phone # +32 (0)2 555 4185

Gilbert Vassart pioneered the use of molecular genetics approaches to solve endocrinology issues. Over the past three decades his group identified gain- and loss-of-function mutations in several endocrine disease and cloned a host of G protein-coupled receptors (GPCRs), opening the way to what has been coined “reverse pharmacology”. In collaboration with Marc Parmentier, this led to the deorphanization of several GPCRs, including CCR5, the main co-receptor for infection by HIV-1.
See: Pubmed

Morgane Leprovots: technician


She obtained a bachelor’s degree in Cellular biology, genetics, microbiology and physiology in 2011 at the University of Rennes (France) and a vocational bachelor’s in biology in 2012 at the IUT Tours (France). She joined our lab in September 2013.

Maryam Marefati: PhD student


She obtained a bachelor/master’s degree in biology-Zoology in 2011 from Ferdowsi University of Mashhad (Iran) and a Master of Molecular Biology in 2016 from the Vrije Universiteit Brussels. She has joined our laboratory in October 2017 to study regeneration processes in adult gastrointestinal tissues.

Gilles Dinsart: PhD student


He obtained a master’s degree in Biomedical Sciences in 2018 from the University of Namur. He has joined our laboratory in December 2018 to study the role of GPCRs expressed by gut epithelium in global metabolic regulation.

Alia Hadefi: PhD student


She is an MD in Gastroenterology from the University Libre de Bruxelles (Experimental Gastroenterology Laboratory) who has joined our laboratory in October 2018 to study the influence of intestinal epithelial resurfacing in patients with liver diseases.

Kawthar Mohamed: lab technician

She obtained a laboratory technician diploma in September 2020 and joined the group in February 2021.

 

 

 

Publications

Cold atmospheric plasma differentially affects cell renewal and differentiation of stem cells and APC-deficient-derived tumor cells in intestinal organoids. Alia Hadefi, Morgane Leprovots, Max Thulliez, Orianne Bastin, Anne Lefort, Frederick Libert, Antoine Nonclercq, Alain Delchambre, Francois Reniers, Jacques Deviere, Marie-Isabelle Garcia. bioRxiv 2021.10.13.464287; doi: https://doi.org/10.1101/2021.10.13.464287

LGR4 deficiency results in delayed puberty through impaired Wnt/β-catenin signaling Alessandra Mancini, Sasha R. Howard, Federica Marelli, Claudia P. Cabrera, Michael R. Barnes, Michael J.E. Sternberg, Morgane Leprovots, Irene Hadji, demetriou, Elena Monti, Alessia David, Karoliina Wehkalampi, Roberto Oleari, Antonella Lettieri, Valeria Vezzoli, Gilbert Vassart, Anna Cariboni, Marco Bonomi, Marie Isabelle Garcia, Leonardo Guasti, and Leo Dunkel. CI Insight. 2020;5(11):e133434

Lgr5 controls extracellular matrix production by stem cells in the developing intestine. Fernandez-Vallone V., Leprovots M., Gerbier R., Ribatallada-Soriano D., Lefort A., Libert F., Vassart G., Garcia MI. EMBO Rep, vol. 3, no. n/a, p. 038, May 2020.

LGRs receptors as peculiar GPCRs involved in cancer (Review). Garcia MI. J Stem Cell Res Med 2017, doi: 10.15761/JSCRM.1000116.

Ex vivo culture of gastric spheroids. Fernandez Vallone V., Leprovots M., Vassart G and Garcia MI. Bio-protocols . 2017. DOI 10.21769/2089.

Ex vivo culture of adult antral glands. Fernandez Vallone V., Leprovots M., Vassart G and Garcia MI. Bio-protocols. 2017. DOI 10.21769/2088.

LGR4 and LGR5 Regulate Hair Cell Differentiation in the Sensory Epithelium of the Developing Mouse Cochlea. Zak, Magdalena; Van Oort, Thys; Hendriksen, Ferry G; Garcia, Marie-Isabelle; Vassart, Gilbert; Grolman, Wilko. Front Cell Neurosci. 2016; 10: 186. doi: 10.3389/fncel.2016.00186 PMCID: PMC4988241

Stem Cells in Adult Homeostasis, Regeneration and Tissue Development of the Digestive Tract Epithelium. Valeria Fernandez Vallone and Marie-Isabelle Garcia. Int J Stem Cell Res Ther 2016, 3:038 Volume 3 | Issue 2 ISSN: 2469-570X

Building and rebuilding gastric epithelium: Trop2 as a common denominator. Valeria Fernandez Vallone and Marie-Isabelle Garcia. Atlas of Science, another view on science. Published online August 15th, 2016.

Trop2 marks transient gastric fetal epithelium and adult regenerating cells after epithelial damage: Fernandez Vallone V, Leprovots M, Strollo S, Vasile G, Lefort A, Libert F, Vassart G, Garcia MI.
Development. 2016 May 1;143(9):1452-63. doi: 10.1242/dev.131490. Epub 2016 Mar 17.

Identification of Lgr5-independent spheroid-generating progenitors of the mouse fetal intestinal epithelium: Mustata RC, Vasile G, Fernandez-Vallone V, Strollo S, Lefort A, Libert F, Monteyne D, Pérez-Morga D, Vassart G, Garcia MI. Cell Rep. 2013 Oct 31;5(2):421-32.

Identification des progéniteurs de l’épithélium intestinal foetal: M/S médecine/sciences. 2014 4:353-355. Garcia MI, Vassart G.

Chapter entitled :”Discovery and Characterization of Leucine-Rich Repeat-Containing G Protein-Coupled Receptors from the book “The Genetics of G Protein-Coupled Receptors: Methods for the Post-Genomic Era” edited by Craig W. Stevens, PhD; Springer Science+Business Media, LLC; Humana Press. MI Garcia, V. Fernandez-Vallone and G. Vassart.

Lgr4 is required for Paneth cell differentiation and maintenance of intestinal stem cells ex vivo. Mustata RC, Van Loy T, Lefort A, Libert F, Strollo S, Vassart G, Garcia MI. EMBO Rep. 2011 Jun;12(6):558-64.

LGR5 deficiency deregulates Wnt signaling and leads to precocious Paneth cell differentiation in the fetal intestine. Garcia MI, Ghiani M, Lefort A, Libert F, Strollo S, Vassart G. Dev Biol. 2009 Jul 1;331(1):58-67.

Three-dimensional reconstruction of efferent ducts in wild-type and Lgr4 knock-out mice. Lambot MA, Mendive F, Laurent P, Van Schoore G, Noël JC, Vanderhaeghen P, Vassart G. Anat Rec (Hoboken). 2009 Apr;292(4):595-603.

Defective postnatal development of the male reproductive tract in LGR4 knockout mice. Mendive F, Laurent P, Van Schoore G, Skarnes W, Pochet R, Vassart G. Dev Biol. 2006 Feb 15;290(2):421-34.

Expression pattern of the orphan receptor LGR4/GPR48 gene in the mouse. Van Schoore G, Mendive F, Pochet R, Vassart G. Histochem Cell Biol. 2005 Jul;124(1):35-50.

Drosophila molting neurohormone bursicon is a heterodimer and the natural agonist of the orphan receptor DLGR2. Mendive FM, Van Loy T, Claeysen S, Poels J, Williamson M, Hauser F, Grimmelikhuijzen CJ, Vassart G, Vanden Broeck J. FEBS Lett.2005 Apr 11;579(10):2171-6.