Gut stem cells in tissue renewal and disease: methods, markers, and myths

Homeostasis in adult tissue is maintained by the activity of a minor population of long-lived resident stem cells. These adult stem cells are defined by two essential attributes, self-renewal and multipotency, and their physiological activity is regulated by a specialized microenvironment, the stem cell niche. These adult stem cells are generally considered to divide infrequently, and cell expansion is mainly achieved through the rapid proliferation of transit amplifying progenitors before they undergo terminal differentiation. Organs that operate in abrasive environments, such as the mucosa of the skin, intestine, and stomach, display a higher tissue turnover rate, which consequently places them at higher risk of developing cancer. Indeed, colorectal cancer (CRC) is one of the most frequent cancers worldwide, with over a million new cases every year. Our understanding of stem cell function in tissue homeostasis and their potential role in cancer development has been greatly hampered by the lack of reliable specific biomarkers, but recent discoveries of membrane bound biomarkers promise great progress in the field. Here we review the current advances toward identifying the stem cells of the gastrointestinal tract and in understanding their microenvironmental regulation, and also discuss their implications for human cancer.