MCB Joint Seminar Series: Miyeko D Mana

Adult tissue stem cells possess the remarkable capacity for self-renewal, differentiation, and lifelong persistence, enabling tissues to maintain homeostasis while adapting to changing physiological and environmental demands. These properties are tightly coordinated by metabolic, transcriptional, and epigenetic programs, and disruption of this regulatory balance can compromise tissue function and contribute to diseases such as cancer.

The mammalian intestine provides a powerful system for understanding how environmental inputs intersect with stem cell regulation. As the primary interface between dietary exposure and nutrient uptake, the intestinal epithelium undergoes continuous and rapid renewal driven by intestinal stem cells (ISCs) residing at the base of the crypt. ISCs generate the diverse epithelial lineages of the intestine while dynamically adjusting their proliferative and differentiation programs in response to dietary and nutrient cues.

Our research seeks to define how stem cells integrate metabolic signals with transcriptional and chromatin regulation to control self-renewal, differentiation, and tissue homeostasis. We leverage dietary interventions as experimental tools to perturb this metabolic–chromatin axis and uncover the molecular mechanisms that establish, maintain, and remodel stem cell states using mouse models, organoids, and human pluripotent stem cell derived organoids. By defining these fundamental mechanisms, our work aims to advance our understanding of stem cell biology and provide a mechanistic foundation for disease prevention and therapeutic intervention. This seminar will focus on two studies: 1) glycosylation regulating lipid metabolism in ISCs, and 2) immune-epithelia interactions driving developmental programming of ISCs in obesogenic conditions.