Intestinal stem cells

Abstract

Intestinal stem cells have been extensively studied in recent years. Through genetic lineage-tracing experiments and transcriptomic approaches, several intestinal stem cell markers have been defined and have contributed to gaining a great deal of insights in the biology of these cells in homeostatic conditions. Here we review the main features of the intestinal epithelium and list the molecular markers that have allowed to identify distinct stem cell populations in the intestinal crypt. We also highlight the major outstanding questions in the field, which still require further investigations, such as: the hierarchical relationship between different subsets of stem cells and uncommitted progenitors; the identity and behavior of colonic and fetal stem cells; the role and composition of the stem cell niche; the control of apical cell migration and of spatial cell distribution along the crypt-villus axis. We then discuss the importance of intestinal stem cells in regenerative medicine and how the advent of stem cell-based intestinal culture systems has paved the way for the development of safe and efficient therapeutic applications of stem cells in regenerative medicine. Finally, we focus on the Notch signalling pathway and describe its fundamental role in stem cell maintenance and control of tissue homeostasis in the intestine of different species. We conclude this review with a brief perspective on the link between normal stem cells and multipotent tumour cells and speculate on the therapeutic consequences of affecting cancer stem cells.