GUT STEM CELL

LAY REVIEW

Summary

Epithelial surfaces of the gastrointestinal tract are under constant cycles of cell proliferation, differentiation, and cell death (apoptosis).  It is believed that the gut stem cells (GSC) are responsible for these cellular events, making it one of the most important elements of the gastrointestinal system (1, 2).  The gut is composed of several organs that extend from the mouth to the anus, but is generally thought of as the stomach, small intestine, and large intestine.  The type and function of each cell varies throughout the different organs in the gut, but many believe that each cell is derived from a common GSC, originating in the endoderm during embryogenesis (3).  Like many other multipotent stem cells, the GSC has the ability to differentiate into various cell lineages, and also has the ability for self renewal (Fig. 1) (4). 

Thus far, scientists have identified to cell markers for GSCs: Musashi-1 (Msi-1) and Hairy and Enhancer of Split homologue-1 (Hes-1) (5, 6).  The identification of cell markers has allowed scientists to obtain further knowledge regarding GSC locations and migration patterns. 

GSCs in the large and small intestine are located in the villus crypt base (6, 7), while GSCs in the stomach can be found in the neck/isthmus region of the tubular glands (2).  It is believed that the intestinal crypts and tubular glands contain myo-epithelial fibroblasts that help provide the necessary niche for GSCs by secreting various mediators and growth factors (2, 8). 

Rapid turnover of the epithelium makes the gut significantly more susceptible to developing gastrointestinal cancers.  Several forms of gastrointestinal cancer are found in the gut.  Colon cancer is the second most common cause of cancer-related death (9).  The constant differentiation of GSCs in the intestine is thought to be one of the primary reasons behind the intestinal epithelium’s high susceptibility to cancer (8).  Also, disruptions and mutations that cause errors in GSC signaling pathways have been shown to lead to several forms of gastrointestinal cancers, including stomach and colon cancers (10).  Once a mutation occurs and a GSC starts differentiating into malignant cells, the constant renewal of epithelial cells increases the probability of future mutations.  Therefore, GSCs have vast therapeutic potential in clinical settings, but further research must be performed before their potential can be translated into clinical applications.

Figure 1: GSC hierarchy showing asymmetrical stem cell division.

Fig. 2 GSCs in the intestine reside at the base of the crypt; once GSCs begin to differentiate the cells rise to the top.  Hes-1 and Msi-1 together are believed to be markers of GSCs, while Hes-1 alone may be a marker of GSCs that have begun to differentiate.

References

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9. Nelson H, Petrelli N, Carlin A et. al. Guidelines 2000 for colon and rectal cancer surgery. J Natl Cancer Inst 2001;93:583-96.
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12. Munoz NM, Upton M, Rojas A et. al. Transforming growth factor beta receptor type II inactivation induces the malignant transformation of intestinal neoplasms initiated by Apc mutation. Cancer Res 2006;66:9837-44.
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Summarized by: Manocchio J, Rana R, Reddy B, Stem Cell Graduate Course, Fall 2006
TA: Shakti Ramkissoon