Molecular mechanisms of intestinal stem cell specification during development
The generation of specific cell types from the intestinal stem cells (ISCs) is determined by the combinatorial actions of diverse signals that impose developmental restrictions on progenitor cells. Transcription factors and histone-modifying complexes are instrumental for the maintenance of stem cell potential and for a stable determination of cell fate. On the other hand, dynamic changes in DNA and histone modifications at critical gene loci are required during differentiation of stem cells to more specialized cell types. To elucidate the molecular pathways regulating formation, maintenance and differentiation the ISCs we are conducting ex-vivo based screens using crypt-villus organoid cultures. We are also interested in how environmental cues (microbiota) may influence the maintenance and differentiation of the adult ISCs in health and after induced injury. A better understanding of these processes may lead to development of novel stem cell and regenerative medicine therapies.