ABSTRACT
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 establish-
ing 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.