immune regulation of intestinal stem cells

The gut mucosa is a complex tissue in which many cellular components interact to achieve gut homeostasis. A single layer of intestinal epithelial cells (IECs) provides an interface for immune cells to detect and respond to environmental substances, which is dominated by a variety of gut-resident microbial species and their products. The gut epithelium constantly regenerates by rapid proliferation and differentiation to maintain barrier integrity and tissue homeostasis. This process is initiated by intestinal stem cells (ISCs), which give rise to committed progenitors that, in turn, differentiate to specific IEC types. ISC maintenance depends on external signals from an ecosystem of microbial and non-epithelial cells found in the gut ISC niche. Studying adult stem cells within a tissue is a difficult task, but investigating microbial and immune-related cues regulating these cells adds an additional layer of complexity. Recent advances in mouse genetics and single-cell genomics enable us to examine these elusive interactions. In this talk, I will introduce a novel ISC sensing concept of microbial molecules resulting in a feed-forward loop of antimicrobial peptide (AMP) secreting cell differentiation to keep the microbiota of the gut in check. To do so, we utilized ex vivo spheroids and monolayers to test ISC sensing and in vivo mouse models to better understand the function of ISC sensing. Overall, this study will advance our understanding of adult stem cell biology and shed light on microbial signals controlling ISC fate in the gut.