Lineage tracking, regulation, and behaviors of intestinal stem cells

Stem cells hold the promise of the development of novel therapies for treating diseases. Unfortunately, the use and study of embryonic stem cells are currently clouded by ethical controversy. Adult stem cells offer a unique alternative in that they may be isolated, studied, or manipulated without harming the donor. However, the adult stem-cell field is still in its infancy. Several obstacles for manipulation of adult stem cells exist. First, the ability to identify most adult stem cells is impeded by lack of stem-cell-exclusive markers. Second, in vitro systems for manipulating adult stem-cell populations are not well defined for all tissues. Third, the ability to reconstitute stem-cell function in vivo has not been demonstrated for most organs. Finally, our understanding of how adult stem cells are regulated within their niche is just beginning to be elucidated. Next to the hematopoietic stem cell, epithelial stem cells are one of the most widely studied adult stem-cell population. Even so, the diversity between epithelial functions in different organs makes it difficult to determine if common themes exist in regulating these related stem cells. In the intestine, insights into the stem-cell behavior have been primarily inferred by lineage tracking experiments. These studies have been invaluable in establishing the foundation for our understanding of intestinal stem cells. This chapter reviews the historical use of lineage tracking of intestinal epithelial cells and presents recent findings in our understanding of regulation of stem cells in order to anticipate where the intestinal stem-cell field is heading in the future.