Early-life environmental imprinting on adult stem cells – ENVIRO-print

The concept of stem cell “pre-programming” or “stem cell memory” is defined by the long-lasting alteration of stem cell activity after past, yet resolved, environmental challenge to the tissue. Epigenetic memory has been described in mammals after inflammation of skin epithelial stem cells, in hematopoietic stem cells, and in Drosophila sensory neurons in response to a high sugar diet. While these studies indicate important functions of stem cell pre-programming, how the nutritional environment imprints on stem and progenitor cells is largely unknown as is how the microbiome - an important internal and nutrition-related environmental parameter- contributes to this process. We plan to address this question in this proposed project, ENVIRO-print, using the adult fly intestine as a model. ENVIRO-print will be organized around 3 questions. 1. How does early-life diet and microbiome affect the transcriptome and epigenome of adult midgut precursor cells present in the larval gut? 2. What is the impact of early-life environment on the epigenome of adult stem cells and gut epithelia? 3. What are the lasting effects of early-life environment on adult tumorigenic growth, sensitivity to chronic inflammation, and regenerative potential of the digestive tracts?