During intestinal organogenesis, equipotent epithelial progenitors mature into phenotypically distinct stem cells that are responsible for lifelong maintenance of the tissue. While the morphological changes associated with the transition are well characterized, the molecular mechanisms underpinning the maturation process are not fully understood. In this project, the main goal was to define transcriptional and epigenetic landscapes that define the embryonic and adult cellular states in order to identify cell-intrinsic mechanisms regulating tissue maturation.
This project generated a comprehensive datasets that provide a framework for investigation of determinants of epithelial maturation, allowing scientists in the field to further investigate and better understand the developmental processes and associated congenital disorders of the intestinal epithelium. Given the emerging evidence that similar mechanisms operate in the context of tissue repair and cancer, the findings of the project are also of interest for regenerative medicine and oncology research fields. Finally, the identification cell-intrinsic mechanisms regulating cellular maturation might also assist the development of more robust embryonic stem cell/induced pluripotent stem cell differentiation in vitro protocols, which often result in the generation of immature cell types that are ill-suited for functional studies or cell-replacement therapies for a variety of human disorders.
Thus, in summary, the knowledge generated in the project might assist the future development of more effective therapies for a variety of conditions affecting the gastrointestinal tract (e.g congenital disorders, inflammatory bowel diseases, colorectal cancer) and, therefore, benefit society at large.
