Searching for adult stem cells in the intestine

Abstract

The epithelium of the small intestine is the most rapidly self‐renewing tissue of mammals. Vigorous proliferation of progenitor cells occurs in crypts, while their differentiated offspring leaves the crypts and travels up the flanks of the villi to suffer death by apoptosis at villus tips 3 days later (Fig 1). The crypts have long been assumed to harbour functional stem cells. » The crypts have long been assumed to harbour functional stem cells. « Yet, the absence of unique molecular markers has hampered their definitive identification. Although there has been agreement that crypts contain 4–6 independent stem cells, two hypotheses exist regarding their exact identity and location. The small intestinal crypt is pictured as a tube of proliferating cells bounded from below by Paneth cells (Fig 1A) (Bjerknes & Cheng, 2005). Since the late 1950s, the prevailing hypothesis has proposed that the stem cells reside at position +4 relative to the crypt bottom, while the first three positions are occupied by the terminally differentiated Paneth cells. Potten et al have provided experimental support for this model, by demonstrating that label‐retaining, radiation‐sensitive cells reside specifically at the +4 position (Potten, 1977; Potten et al, 1974, confirm 12 and 13). The second, more recent hypothesis is based on the identification of the crypt base columnar (CBC) cells, small cycling cells inconspicuously hidden between the Paneth cells (Cheng & Leblond, 1974a) (Fig 1A). The proposal was initially based on morphological features of these cells (Cheng & Leblond, 1974b), but clonal marking techniques have later led Leblond, Cheng and Bjerknes to propose that the CBC cells represent the true stem cells (Bjerknes & Cheng, 1981a, 1981b, 1999). Figure 1. Stem cells of the small intestine .