Thesis: Pelvic cancers are highly prevalent and are mainly treated with radiotherapy. While radiation therapy may control the tumor, it can also cause damage to surrounding healthy tissue, leading to disabling complications defined as a disease “pelvic radiation disease” (PRD). Currently, there is no curative treatment for this fibrosing pathology. The aims of this project are to study the colonic microenvironment after irradiation with a view to identify new therapeutic targets to improve the management of the colonic sequelae of PRD. For this project, a mouse model developing fibrosing colonic lesions similar to those observed in PRD patients was developed. It consists of localized colorectal irradiation with a single dose of 26Gy. We defined 2 post-irradiation study periods: 2 weeks to study the acute effects of irradiation and the regeneration process, and 12 weeks to study fibrosis. Histological studies characterized the mucosal lesions, with a deep ulcer at 2 weeks and fibrous remodeling at 12 weeks. At the 2 time points studied, an increased and disorganized proliferative process was observed, as well as a deficit in epithelial junction proteins, suggesting a defect in barrier function. We demonstrated the impact of the irradiated colonic microenvironment on epithelial proliferation and differentiation processes using a co-culture system with colonic organoids monitored by video microscopy. Our results validated in vivo observations of increased organoid proliferation in the presence of stroma derived from mice 12 weeks post-irradiation.To characterize stromal mesenchymal cells after irradiation, single-cell RNA sequencing experiments (using EpCAM-CD45-sorted colonic cells and from whole colon) and spatial transcriptomics were performed. They revealed a new marker, Edil3, specific for the major stromal population of the colon. This new marker allowed us to better characterize this cell population in terms of function and localization in the healthy colon. We proposed to call them mesitocytes. In the early stages, we found that this population could differentiate towards a pro-inflammatory profile called "IAF" for "Inflammation-Associated Fibroblasts". We also observed increased expression of transcripts involved in critical functions such as epithelial homeostasis, angiogenesis and inflammation by the majority of mesenchymal cells. The results demonstrate the importance of proliferative molecular signals from lymphatic endothelial cells and smooth muscle cells, particularly Grem-1. Analysis of the chronic phase after irradiation confirms the increase in proliferative signals from stromal cells. In addition, a new fibroblast cell type associated with fibrosis was observed, characterized by a transcriptional profile different from that of the IAF observed in the early phase. The study of the effects of irradiation on the epithelial compartment revealed significant changes in the colonocyte population and the appearance of epithelial cells with a "revival" phenotype, already described in the literature. Interestingly, these populations have specific localizations in regenerating crypts. We also established the importance of genes such as Lypd8 and Anxa1 in the progression of proliferating epithelial cells towards a "revival" phenotype. Interesting observations from spatial transcriptomic analyses also allow us to hypothesize the role of immune cells in the epithelial regeneration process.