Description du projet
Séquençage in situ pour cartographier les interactions cellulaires dans la muqueuse intestinale
Dans des conditions physiologiques, l’épithélium intestinal constitue une barrière physique dynamique servant de première ligne de défense immunitaire. Une monocouche de cellules épithéliales intestinales spécialisées endommagée induit une perturbation de l’homéostasie immunitaire intestinale et conduit à des maladies inflammatoires de l’intestin (MII), comme la colite ulcéreuse et la maladie de Crohn. Compte tenu de l’augmentation de l’incidence des MII dans les sociétés modernes, les scientifiques du projet GUTMAPS, financé par l’UE, étudieront les tissus intestinaux dans une résolution sans précédent. Pour ce faire, ils effectueront un séquençage in situ pour profiler les cellules individuelles, cartographier les interactions cellule-cellule et aider à créer une meilleure compréhension de cet organe en matière de santé et de maladie.
Objectif
The intestinal epithelium is the first line of defence of the mucosal immune system because it acts as a dynamic physical barrier segregating the luminal content from the underlying mucosal tissue. This barrier is mainly formed by a monolayer of specialised intestinal epithelial cells (IECs) that are crucial in maintaining intestinal homeostasis. Damage to this epithelial layer can increase intestinal permeability and lead to abnormalities in interactions between IECs, stromal cells and immune cells in the underlying lamina propria thereby disturbing the intestinal immune homeostasis, all of which are a hallmark of several intestinal disorders including inflammatory bowel diseases (IBD). Ulcerative colitis (UC) and Crohn’s disease (CD) are the two major forms of IBD, affecting an estimated 4 million people in the United States and Europe and have a rising incidence in the developing world. Recent single cell RNA seq (scRNAseq) studies of the intestine have allowed us to understand this organ in unprecedented detail, however, such studies still require the dissociation of tissue and loss of spatial resolution. With this project, I would like to take advantage of recent advances in in-situ sequencing to study intestinal tissue in toto and by combining this with the available scRNA-seq data, generate spatial maps of the intestine (GUTMAPS). The results obtained here will allow us to look at tissue composition and cell-cell interactions with unprecedented resolution in normal and diseased mucosa.
Champ scientifique
- natural sciencesearth and related environmental sciencesphysical geographycartography
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- medical and health sciencesbasic medicineimmunology
- natural sciencesbiological sciencesgeneticsRNA
- medical and health sciencesbasic medicinephysiologyhomeostasis
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
3015 GD Rotterdam
Pays-Bas